Menopause is a consequence of the normal aging process in women. This fact implies that the physiological and biochemical alterations resulting from menopause often blur with those from the aging process. It is thought that menopause in women presents a higher risk for cardiovascular disease although the precise mechanism is still under discussion. The postmenopause lipid profile is clearly altered, which can present a risk factor for cardiovascular disease. Due to the role of mitochondria in fatty acid oxidation, alterations of the lipid profile in the menopausal women will also influence mitochondrial fatty acid oxidation fluxes in several organs. In this paper, we propose that alterations of mitochondrial bioenergetics in the heart, consequence from normal aging and/or from the menopausal process, result in decreased fatty acid oxidation and accumulation of fatty acid intermediates in the cardiomyocyte cytosol, resulting in lipotoxicity and increasing the cardiovascular risk in the menopausal women. 1. Menopause: A Burden for Aging Women Menopause is one of the most critical periods in women’s life. Although being a natural biological process that occurs with aging, physiological alterations observed during this period can be challenging. Caused by a reduced secretion of ovarian hormones estrogen and progesterone after depletion of the storage of ovarian follicles, menopause defines the end of women menstrual cycle and their natural fertility. On average, spontaneous or natural menopause occurs around the early 50s and is confirmed after 12 months of nonpathological amenorrhoea. However, when premature ovarian failure (POF) occurs before the 40s due to pathological causes, an early or premature menopause can be induced, which is thus disconnected from the aging process properly said. When a bilateral oophorectomy is necessary, menopause occurs immediately without women experiencing the gradual transition of perimenopause. Chemotherapy can also provoke a permanent damage in ovaries and induces menopause per se [1]. Women who experience an early menopause are more susceptible to certain health problems, such as osteoporosis and heart diseases, since they spend more time in their lives without the benefits of estrogens. POF can also be temporary (temporary menopause) induced by high levels of stress, excessive exercising and/or dieting, and by medications used to treat fibroids [2] and endometriosis [3]. However, as soon as women adopt a healthier life style or stop medication, the ovaries may resume normal production of hormones. Normally, menopausal
References
[1]
A. M. Gordon, S. Hurwitz, C. L. Shapiro, and M. S. Leboff, “Premature ovarian failure and body composition changes with adjuvant chemotherapy for breast cancer,” Menopause, vol. 18, no. 11, pp. 1244–1248, 2011.
[2]
M. Shozu, K. Murakami, and M. Inoue, “Aromatase and leiomyoma of the uterus,” Seminars in Reproductive Medicine, vol. 22, no. 1, pp. 51–60, 2004.
[3]
A. E. Schindler, “Dienogest in long-term treatment of endometriosis,” International Journal of Women's Health, vol. 3, pp. 175–184, 2011.
[4]
D. Kaleta, B. Usidame, and K. Polańska, “Tobacco advertisements targeted on women: creating an awareness among women,” Central European Journal of Public Health, vol. 19, no. 2, pp. 73–78, 2011.
[5]
J. C. Stevenson, “A woman's journey through the reproductive, transitional and postmenopausal periods of life: impact on cardiovascular and musculo-skeletal risk and the role of estrogen replacement,” Maturitas, vol. 70, no. 2, pp. 197–205, 2011.
[6]
F. Kronenberg, “Menopausal hot flashes: a review of physiology and biosociocultural perspective on methods of assessment,” Journal of Nutrition, vol. 140, no. 7, pp. 1380S–1385S, 2010.
[7]
R. Green and N. Santoro, “Menopausal symptoms and ethnicity: the study of Women's Health Across the Nation,” Women's Health, vol. 5, no. 2, pp. 127–133, 2009.
[8]
H. D. Nelson, “Menopause,” The Lancet, vol. 371, no. 9614, pp. 760–770, 2008.
[9]
S. L. Dormire, “The potential role of glucose transport changes in hot flash physiology: a hypothesis,” Biological Research for Nursing, vol. 10, no. 3, pp. 241–247, 2009.
[10]
M. Panjari and S. R. Davis, “Vaginal DHEA to treat menopause related atrophy: a review of the evidence,” Maturitas, vol. 70, no. 1, pp. 22–25, 2011.
[11]
B. Frenkel, A. Hong, S. K. Baniwal et al., “Regulation of adult bone turnover by sex steroids,” Journal of Cellular Physiology, vol. 224, no. 2, pp. 305–310, 2010.
[12]
P. Babaei, R. Mehdizadeh, M. M. Ansar, and A. Damirchi, “Effects of ovariectomy and estrogen replacement therapy on visceral adipose tissue and serum adiponectin levels in rats,” Menopause International, vol. 16, no. 3, pp. 100–104, 2010.
[13]
S. L. Palin, P. G. McTernan, L. A. Anderson, D. W. Sturdee, A. H. Barnett, and S. Kumar, “17β-Estradiol and anti-estrogen ICI: compound 182,780 regulate expression of lipoprotein lipase and hormone-sensitive lipase in isolated subcutaneous abdominal adipocytes,” Metabolism, vol. 52, no. 4, pp. 383–388, 2003.
[14]
H. Szafran and W. Smielak-Korombel, “The role of estrogens in hormonal regulation of lipid metabolism in women,” Przegla？d lekarski, vol. 55, no. 5, pp. 266–270, 1998.
[15]
T. Yoshida, K. Takahashi, H. Yamatani, K. Takata, and H. Kurachi, “Impact of surgical menopause on lipid and bone metabolism,” Climacteric, vol. 14, no. 4, pp. 445–452, 2011.
[16]
C. Vassalle, A. Mercuri, and S. Maffei, “Oxidative status and cardiovascular risk in women: keeping pink at heart,” World Journal of Cardiology, vol. 1, no. 1, pp. 26–30, 2009.
[17]
I. M. Fearon and S. P. Faux, “Oxidative stress and cardiovascular disease: novel tools give (free) radical insight,” Journal of Molecular and Cellular Cardiology, vol. 47, no. 3, pp. 748–381, 2009.
[18]
K. Tolfrey, “American Heart Association guidelines for preventing heart disease in women: 2007 Update,” Physician and Sportsmedicine, vol. 38, no. 1, pp. 162–164, 2010.
[19]
“Third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report,” Circulation, vol. 106, no. 25, pp. 3143–3421, 2002.
[20]
L. Mosca, S. M. Grundy, D. Judelson, et al., “AHA/ACC scientific statement: consensus panel statement. Guide to preventive cardiology for women. American Heart Association/American College of Cardiology,” Journal of American College of Cardiology, vol. 33, no. 6, pp. 1751–1755, 1999.
[21]
L. Mosca, S. M. Grundy, D. Judelson, et al., “Guide to preventive cardiology for women. AHA/ACC scientific statement consensus panel statement,” Circulation, vol. 99, no. 18, pp. 2480–2484, 1999.
[22]
L. Mosca, H. Mochari-Greenberger, R. J. Dolor, L. K. Newby, and K. J. Robb, “Twelve-year follow-up of American women's awareness of cardiovascular disease risk and barriers to heart health,” Circulation: Cardiovascular Quality and Outcomes, vol. 3, no. 2, pp. 120–127, 2010.
[23]
H. Tunstall-Pedoe, “Myth and paradox of coronary risk and the menopause,” Lancet, vol. 351, no. 9113, pp. 1425–1427, 1998.
[24]
D. J. Lerner and W. B. Kannel, “Patterns of coronary heart disease morbidity and mortality in the sexes: a 26-year follow-up of the Framingham population,” American Heart Journal, vol. 111, no. 2, pp. 383–390, 1986.
[25]
G. M. Rosano, C. Vitale, G. Marazzi, and M. Volterrani, “Menopause and cardiovascular disease: the evidence,” Climacteric, vol. 10, no. 1, pp. 19–24, 2007.
[26]
J. F. Reckelhoff and C. Maric, “Editorial: sex and gender differences in cardiovascular-renal physiology and pathophysiology,” Steroids, vol. 75, no. 11, pp. 745–746, 2010.
[27]
V. Bittner, “Menopause, age, and cardiovascular risk: a complex relationship,” Journal of the American College of Cardiology, vol. 54, no. 25, pp. 2374–2375, 2009.
[28]
E. S. Kim and V. Menon, “Status of women in cardiovascular clinical trials,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 29, no. 3, pp. 279–283, 2009.
[29]
M. Coylewright, J. F. Reckelhoff, and P. Ouyang, “Menopause and hypertension: an age-old debate,” Hypertension, vol. 51, no. 4, pp. 952–959, 2008.
[30]
S. M. Grundy, “Guidelines for cholesterol management: recommendations of the National Cholesterol Education Program's Adult Treatment Panel II,” Heart Disease and Stroke, vol. 3, no. 3, pp. 123–127, 1994.
[31]
J. S. Hong, S. W. Yi, H. C. Kang et al., “Age at menopause and cause-specific mortality in South Korean women: kangwha Cohort Study,” Maturitas, vol. 56, no. 4, pp. 411–419, 2007.
[32]
F. B. Hu, F. Grodstein, C. H. Hennekens et al., “Age at natural menopause and risk of cardiovascular disease,” Archives of Internal Medicine, vol. 159, no. 10, pp. 1061–1066, 1999.
[33]
B. L. Haddock, H. P. Hopp Marshak, J. J. Mason, and G. Blix, “The effect of hormone replacement therapy and exercise on cardiovascular disease risk factors in postmenopausal women,” Sports Medicine, vol. 29, no. 1, pp. 39–49, 2000.
[34]
K. A. Matthews, S. L. Crawford, C. U. Chae et al., “Are changes in cardiovascular disease risk factors in midlife women due to chronological aging or to the menopausal transition?” Journal of the American College of Cardiology, vol. 54, no. 25, pp. 2366–2373, 2009.
[35]
E. Barrett-Connor, “Sex differences in coronary heart disease: why are women so superior? The 1995 Ancel Keys Lecture,” Circulation, vol. 95, no. 1, pp. 252–264, 1997.
[36]
H. S. Kok, K. M. van Asselt, Y. T. van der Schouw et al., “Heart disease risk determines menopausal age rather than the reverse,” Journal of the American College of Cardiology, vol. 47, no. 10, pp. 1976–1983, 2006.
[37]
L. Mosca, C. L. Banka, E. J. Benjamin et al., “Evidence-based guidelines for cardiovascular disease prevention in women: 2007 Update,” Journal of the American College of Cardiology, vol. 49, no. 11, pp. 1230–1250, 2007.
[38]
C. Vassalle, L. Petrozzi, N. Botto, M. G. Andreassi, and G. C. Zucchelli, “Oxidative stress and its association with coronary artery disease and different atherogenic risk factors,” Journal of Internal Medicine, vol. 256, no. 4, pp. 308–315, 2004.
[39]
E. Schwedhelm, A. Bartling, H. Lenzen, et al., “Urinary 8-iso-prostaglandin F2 α as a risk marker in patients with coronary heart disease: a matched case-control study,” Circulation, vol. 109, no. 7, pp. 843–848, 2004.
[40]
L. Baker, K. K. Meldrum, M. Wang et al., “The role of estrogen in cardiovascular disease,” Journal of Surgical Research, vol. 115, no. 2, pp. 325–344, 2003.
[41]
O. C. Gebara, M. A. Mittleman, P. Sutherland et al., “Association between increased estrogen status and increased fibrinolytic potential in the Framingham Offspring Study,” Circulation, vol. 91, no. 7, pp. 1952–1958, 1995.
[42]
G. A. Colditz, W. C. Willett, M. J. Stampfer, et al., “Menopause and the risk of coronary heart disease in women,” New England Journal of Medicine, vol. 316, no. 18, pp. 1105–1110, 1987.
[43]
W. J. Mack, C. C. Slater, M. Xiang, D. Shoupe, R. A. Lobo, and H. N. Hodis, “Elevated subclinical atherosclerosis associated with oophorectomy is related to time since menopause rather than type of menopause,” Fertility and Sterility, vol. 82, no. 2, pp. 391–397, 2004.
[44]
A. M. Shearman, L. A. Cupples, S. Demissie et al., “Association between estrogen receptor α gene variation and cardiovascular disease,” Journal of the American Medical Association, vol. 290, no. 17, pp. 2263–2270, 2003.
[45]
F. Grodstein, M. J. Stampfer, J. E. Manson et al., “Postmenopausal estrogen and progestin use and the risk of cardiovascular disease,” New England Journal of Medicine, vol. 335, no. 7, pp. 453–461, 1996.
[46]
D. Grady, S. M. Rubin, D. B. Petitti et al., “Hormone therapy to prevent disease and prolong life in postmenopausal women,” Annals of Internal Medicine, vol. 117, no. 12, pp. 1016–1037, 1992.
[47]
T. W. Meade and A. Berra, “Hormone replacement therapy and cardiovascular disease,” British Medical Bulletin, vol. 48, no. 2, pp. 276–308, 1992.
[48]
K. M. Randell, R. J. Honkanen, H. Kr？ger, and S. Saarikoski, “Does hormone-replacement therapy prevent fractures in early postmenopausal women?” Journal of Bone and Mineral Research, vol. 17, no. 3, pp. 528–533, 2002.
[49]
B. Ettinger, D. M. Black, B. H. Mitlak, et al., “Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) investigators,” Journal of the American Medical Association, vol. 282, no. 7, pp. 637–645, 1999.
[50]
B. E. Henderson, A. Paganini-Hill, and R. K. Ross, “Decreased mortality in users of estrogen replacement therapy,” Archives of Internal Medicine, vol. 151, no. 1, pp. 75–78, 1991.
[51]
T. L. Bush, E. Barrett-Connor, L. D. Cowan, et al., “Cardiovascular mortality and noncontraceptive use of estrogen in women: results from the Lipid Research Clinics Program Follow-up Study,” Circulation, vol. 75, no. 6, pp. 1102–1109, 1987.
[52]
T. L. Bush, L. D. Cowan, E. Barrett Connor, et al., “Estrogen use and all-cause mortality. Preliminary results from the Lipid Research Clinics Program Follow-up study,” Journal of the American Medical Association, vol. 249, no. 7, pp. 903–906, 1983.
[53]
C. Schairer, J. Lubin, R. Troisi, S. Sturgeon, L. Brinton, and R. Hoover, “Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk,” Journal of the American Medical Association, vol. 283, no. 4, pp. 485–491, 2000.
[54]
L. Bergkvist, H. O. Adami, I. Persson, R. Hoover, and C. Schairer, “The risk of breast cancer after estrogen and estrogen-progestin replacement,” New England Journal of Medicine, vol. 321, no. 5, pp. 293–297, 1989.
[55]
J. E. Rossouw, G. L. Anderson, R. L. Prentice et al., “Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women's health initiative randomized controlled trial,” Journal of the American Medical Association, vol. 288, no. 3, pp. 321–333, 2002.
[56]
G. L. Anderson, M. Limacher, A. R. Assaf, et al., “Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial,” Journal of the American Medical Association, vol. 291, no. 14, pp. 1701–1712, 2004.
[57]
A. L. Hersh, M. L. Stefanick, and R. S. Stafford, “National use of postmenopausal hormone therapy: annual trends and response to recent evidence,” Journal of the American Medical Association, vol. 291, no. 1, pp. 47–53, 2004.
[58]
J. E. Rossouw, R. L. Prentice, J. E. Manson et al., “Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause,” Journal of the American Medical Association, vol. 297, no. 13, pp. 1465–1477, 2007.
[59]
S. M. Harman, E. Vittinghoff, E. A. Brinton et al., “Timing and duration of menopausal hormone treatment may affect cardiovascular outcomes,” American Journal of Medicine, vol. 124, no. 3, pp. 199–205, 2011.
[60]
L. Mosca, E. J. Benjamin, K. Berra et al., “Effectiveness-based guidelines for the prevention of cardiovascular disease in women-2011 update: a Guideline from the American Heart Association,” Circulation, vol. 123, no. 11, pp. 1243–1262, 2011.
[61]
M. Pierdominici, E. Ortona, F. Franconi, M. Caprio, E. Straface, and W. Malorni, “Gender specific aspects of cell death in the cardiovascular system,” Current Pharmaceutical Design, vol. 17, no. 11, pp. 1046–1055, 2011.
[62]
A. M. Deschamps, E. Murphy, and J. Sun, “Estrogen receptor activation and cardioprotection in ischemia reperfusion injury,” Trends in Cardiovascular Medicine, vol. 20, no. 3, pp. 73–78, 2010.
[63]
J. S. Juggi, L. J. Hoteit, F. A. Babiker, S. Joseph, and A. S. Mustafa, “Protective role of normothermic, hyperthermic and estrogen preconditioning and pretreatment on tumour necrosis factor-α-induced damage,” Experimental and Clinical Cardiology, vol. 16, no. 2, pp. e5–e10, 2011.
[64]
S. Kanki, V. F. Segers, W. Wu et al., “Stromal cell-derived factor-1 retention and cardioprotection for ischemic myocardium,” Circulation, vol. 4, no. 4, pp. 509–518, 2011.
[65]
C. Huang, H. Gu, Y. Wang, and M. Wang, “Estrogen-induced SDF-1 production is mediated by estrogen receptor-α in female hearts after acute ischemia and reperfusion,” Surgery, vol. 150, no. 2, pp. 197–203, 2011.
[66]
J. Cao, T. Zhu, L. Lu et al., “Estrogen induces cardioprotection in male C57BL/6J mice after acute myocardial infarction via decreased activity of matrix metalloproteinase-9 and increased Akt-Bcl-2 anti-apoptotic signaling,” International Journal of Molecular Medicine, vol. 28, no. 2, pp. 231–237, 2011.
[67]
L. F. Valverdea, F. D. Cedillob, M. L. Ramosa, E. G. Cerveraa, K. Quijanoa, and J. Cordobaa, “Changes induced by estradiol-ethylenediamine derivative on perfusion pressure and coronary resistance in isolated rat heart: l-type calcium channel,” Biomedical Papers, vol. 155, no. 1, pp. 27–32, 2011.
[68]
X. Hu, X. Xu, Z. Lu et al., “AMP activated protein kinase-α2 regulates expression of estrogen-related receptor-α, a metabolic transcription factor related to heart failure development,” Hypertension, vol. 58, no. 4, pp. 696–703, 2011.
[69]
M. S. Mitra, J. D. Schilling, X. Wang et al., “Cardiac lipin 1 expression is regulated by the peroxisome proliferator activated receptor γ coactivator 1α/estrogen related receptor axis,” Journal of Molecular and Cellular Cardiology, vol. 51, no. 1, pp. 120–128, 2011.
[70]
D. E. Masood, E. C. Roach, K. G. Beauregard, and R. A. Khalil, “Impact of sex hormone metabolism on the vascular effects of menopausal hormone therapy in cardiovascular disease,” Current Drug Metabolism, vol. 11, no. 8, pp. 693–714, 2010.
[71]
P. A. Arias-Loza, K. Hu, S. Frantz et al., “Medroxyprogesterone acetate aggravates oxidative stress and left ventricular dysfunction in rats with chronic myocardial infarction,” Toxicologic Pathology, vol. 39, no. 5, pp. 867–878, 2011.
[72]
G. D. Lopaschuk, J. R. Ussher, C. D. Folmes, J. S. Jaswal, and W. C. Stanley, “Myocardial fatty acid metabolism in health and disease,” Physiological Reviews, vol. 90, no. 1, pp. 207–258, 2010.
[73]
R. M. Beadle and M. Frenneaux, “Modification of myocardial substrate utilisation: a new therapeutic paradigm in cardiovascular disease,” Heart, vol. 96, no. 11, pp. 824–830, 2010.
[74]
J. Kerner and C. Hoppel, “Fatty acid import into mitochondria,” Biochimica et Biophysica Acta, vol. 1486, no. 1, pp. 1–17, 2000.
[75]
Y. G. Niu and R. D. Evans, “Very-low-density lipoprotein: complex particles in cardiac energy metabolism,” Journal of Lipid Research, vol. 2011, Article ID 189876, 9 pages, 2011.
[76]
Y. G. Niu, D. Hauton, and R. D. Evans, “Utilization of triacylglycerol-rich lipoproteins by the working rat heart: routes of uptake and metabolic fates,” Journal of Physiology, vol. 558, no. 1, pp. 225–237, 2004.
[77]
M. F. Oliver, “Control of free fatty acids during acute myocardial ischaemia,” Heart, vol. 96, no. 23, pp. 1883–1884, 2010.
[78]
A. Barsotti, A. Giannoni, P. di Napoli, and M. Emdin, “Energy metabolism in the normal and in the diabetic heart,” Current Pharmaceutical Design, vol. 15, no. 8, pp. 836–840, 2009.
[79]
G. J. van der Vusse, M. van Bilsen, J. F. Glatz, D. M. Hasselbaink, and J. J. Luiken, “Critical steps in cellular fatty acid uptake and utilization,” Molecular and Cellular Biochemistry, vol. 239, no. 1-2, pp. 9–15, 2002.
[80]
J. F. Glatz, J. J. Luiken, and A. Bonen, “Involvement of membrane-associated proteins in the acute regulation of cellular fatty acid uptake,” Journal of Molecular Neuroscience, vol. 16, no. 2-3, pp. 123–132, 2001.
[81]
J. F. Glatz, J. J. Luiken, F. A. van Nieuwenhoven, and G. J. van der Vusse, “Molecular mechanism of cellular uptake and intracellular translocation of fatty acids,” Prostaglandins Leukotrienes and Essential Fatty Acids, vol. 57, no. 1, pp. 3–9, 1997.
[82]
A. T. Turer, C. R. Malloy, C. B. Newgard, and M. V. Podgoreanu, “Energetics and metabolism in the failing heart: important but poorly understood,” Current Opinion in Clinical Nutrition and Metabolic Care, vol. 13, no. 4, pp. 458–465, 2010.
[83]
M. E. Young, G. W. Goodwin, J. Ying et al., “Regulation of cardiac and skeletal muscle malonyl-CoA decarboxylase by fatty acids,” American Journal of Physiology: Endocrinology and Metabolism, vol. 280, no. 3, pp. E471–E479, 2001.
[84]
S. Eaton, “Control of mitochondrial β-oxidation flux,” Progress in Lipid Research, vol. 41, no. 3, pp. 197–239, 2002.
[85]
S. Grimbert, C. Fisch, D. Deschamps et al., “Effects of female sex hormones on mitochondria: possible role in acute fatty liver of pregnancy,” American Journal of Physiology, vol. 268, no. 1, pp. G107–G115, 1995.
[86]
R. Sladek, J. A. Bader, and V. Giguère, “The orphan nuclear receptor estrogen-related receptor or α is a transcriptional regulator of the human medium-cha n Acyl coenzyme A dehydrogenase gene,” Molecular and Cellular Biology, vol. 17, no. 9, pp. 5400–5409, 1997.
[87]
L. O. Li, E. L. Klett, and R. A. Coleman, “Acyl-CoA synthesis, lipid metabolism and lipotoxicity,” Biochimica et Biophysica Acta, vol. 1801, no. 3, pp. 246–251, 2010.
[88]
N. A. van Herpen and V. B. Schrauwen-Hinderling, “Lipid accumulation in non-adipose tissue and lipotoxicity,” Physiology and Behavior, vol. 94, no. 2, pp. 231–241, 2008.
[89]
L. S. Szczepaniak, R. G. Victor, L. Orci, and R. H. Unger, “Forgotten but not gone: the rediscovery of fatty heart, the most common unrecognized disease in America,” Circulation Research, vol. 101, no. 8, pp. 759–767, 2007.
[90]
N. M. Borradaile and J. E. Schaffer, “Lipotoxicity in the heart,” Current Hypertension Reports, vol. 7, no. 6, pp. 412–417, 2005.
[91]
L. Zhang, J. R. Ussher, T. Oka, V. J. Cadete, C. Wagg, and G. D. Lopaschuk, “Cardiac diacylglycerol accumulation in high fat-fed mice is associated with impaired insulin-stimulated glucose oxidation,” Cardiovascular Research, vol. 89, no. 1, pp. 148–156, 2011.
[92]
I. Chowdhury, A. Branch, M. Olatinwo, K. Thomas, R. Matthews, and W. E. Thompson, “Prohibitin (PHB) acts as a potent survival factor against ceramide induced apoptosis in rat granulosa cells,” Life Sciences, vol. 89, no. 9-10, pp. 295–303, 2011.
[93]
T. D. Mullen and L. M. Obeid, “Ceramide and apoptosis: exploring the enigmatic connections between sphingolipid metabolism and programmed cell death,” Anti-Cancer Agents in Medicinal Chemistry. In press.
[94]
H. Lee, J. A. Rotolo, J. Mesicek et al., “Mitochondrial ceramide-rich macrodomains functionalize bax upon irradiation,” PLoS ONE, vol. 6, no. 6, article e19783, 2011.
[95]
E. Usta, M. Mustafi, F. Artunc et al., “The challenge to verify ceramide's role of apoptosis induction in human cardiomyocytes—a pilot study,” Journal of Cardiothoracic Surgery, vol. 6, no. 1, article 38, 2011.
[96]
S. A. Novgorodov, Z. M. Szulc, C. Luberto et al., “Positively charged ceramide is a potent inducer of mitochondrial permeabilization,” Journal of Biological Chemistry, vol. 280, no. 16, pp. 16096–16105, 2005.
[97]
M. di Paola, P. Zaccagnino, G. Montedoro, T. Cocco, and M. Lorusso, “Ceramide induces release of pro-apoptotic proteins from mitochondria by either a Ca2+-dependent or a Ca2+-independent mechanism,” Journal of Bioenergetics and Biomembranes, vol. 36, no. 2, pp. 165–170, 2004.
[98]
K. W. Kinnally, P. M. Peixoto, S.-Y. Ryu, and L. M. Dejean, “Is mPTP the gatekeeper for necrosis, apoptosis, or both?” Biochimica et Biophysica Acta, vol. 1813, no. 4, pp. 616–622, 2011.
[99]
S. A. Novgorodov, T. I. Gudz, and L. M. Obeid, “Long-chain ceramide is a potent inhibitor of the mitochondrial permeability transition pore,” Journal of Biological Chemistry, vol. 283, no. 36, pp. 24707–24717, 2008.
[100]
M. A. Cole, A. J. Murray, L. E. Cochlin et al., “A high fat diet increases mitochondrial fatty acid oxidation and uncoupling to decrease efficiency in rat heart,” Basic Research in Cardiology, vol. 106, no. 3, pp. 447–457, 2011.
[101]
N. Li, J. Wang, F. Gao, Y. Tian, R. Song, and S.-J. Zhu, “The role of uncoupling protein 2 in the apoptosis induced by free fatty acid in rat cardiomyocytes,” Journal of Cardiovascular Pharmacology, vol. 55, no. 2, pp. 161–167, 2010.
[102]
L. H. Opie and J. Knuuti, “The adrenergic-fatty acid load in heart failure,” Journal of the American College of Cardiology, vol. 54, no. 18, pp. 1637–1646, 2009.
[103]
J. S. Jaswal, W. Keung, W. Wang, J. R. Ussher, and G. D. Lopaschuk, “Targeting fatty acid and carbohydrate oxidation—a novel therapeutic intervention in the ischemic and failing heart,” Biochimica et Biophysica Acta, vol. 1813, no. 7, pp. 1333–1350, 2011.
[104]
M. J. Romero-Aleshire, M. K. Diamond-Stanic, A. H. Hasty, P. B. Hoyer, and H. L. Brooks, “Loss of ovarian function in the VCD mouse-model of menopause leads to insulin resistance and a rapid progression into the metabolic syndrome,” American Journal of Physiology: Regulatory Integrative and Comparative Physiology, vol. 297, no. 3, pp. R587–R592, 2009.
[105]
F. Pansini, G. Bonaccorsi, F. Genovesi et al., “Influence of estrogens on serum free fatty acid levels in women,” Journal of Clinical Endocrinology and Metabolism, vol. 71, no. 5, pp. 1387–1389, 1990.
[106]
C. A. Derby, S. L. Crawford, R. C. Pasternak, et al., “Lipid changes during the menopause transition in relation to age and weight: the Study of Women's Health Across the Nation,” American Journal of Epidemiology, vol. 169, no. 11, pp. 1352–1361, 2009.
[107]
M. L. Power and J. Schulkin, “Sex differences in fat storage, fat metabolism, and the health risks from obesity: possible evolutionary origins,” British Journal of Nutrition, vol. 99, no. 5, pp. 931–940, 2008.
[108]
T. M. D'Eon, S. C. Souza, M. Aronovitz, M. S. Obin, S. K. Fried, and A. S. Greenberg, “Estrogen regulation of adiposity and fuel partitioning: evidence of genomic and non-genomic regulation of lipogenic and oxidative pathways,” Journal of Biological Chemistry, vol. 280, no. 43, pp. 35983–35991, 2005.
[109]
C. M. Williams, “Lipid metabolism in women,” Proceedings of the Nutrition Society, vol. 63, no. 1, pp. 153–160, 2004.
[110]
A. K. Wong, J. Howie, J. R. Petrie, and C. C. Lang, “AMP-activated protein kinase pathway: a potential therapeutic target in cardiometabolic disease,” Clinical Science, vol. 116, no. 8, pp. 607–620, 2009.
[111]
C.-M. Liou, A.-L. Yang, C.-H. Kuo, H. Tin, C.-Y. Huang, and S.-D. Lee, “Effects of 17β-estradiol on cardiac apoptosis in ovariectomized rats,” Cell Biochemistry and Function, vol. 28, no. 6, pp. 521–528, 2010.
[112]
S. D. Lee, W. W. Kuo, Y. J. Ho et al., “Cardiac Fas-dependent and mitochondria-dependent apoptosis in ovariectomized rats,” Maturitas, vol. 61, no. 3, pp. 268–277, 2008.
[113]
W.-C. Liang and I. Nishino, “State of the art in muscle lipid diseases,” Acta Myologica, vol. 29, no. 2, pp. 351–356, 2010.
[114]
M. J. Bennett, “Pathophysiology of fatty acid oxidation disorders,” Journal of Inherited Metabolic Disease, vol. 33, no. 5, pp. 533–537, 2010.
[115]
K. Begriche, J. Massart, M.-A. Robin, A. Borgne-Sanchez, and B. Fromenty, “Drug-induced toxicity on mitochondria and lipid metabolism: mechanistic diversity and deleterious consequences for the liver,” Journal of Hepatology, vol. 54, no. 4, pp. 773–794, 2011.
[116]
J. A. Bjork, J. L. Butenhoff, and K. B. Wallace, “Multiplicity of nuclear receptor activation by PFOA and PFOS in primary human and rodent hepatocytes,” Toxicology, vol. 288, no. 1–3, pp. 8–17, 2011.
[117]
E. Freneaux, G. Labbe, P. Letteron et al., “Inhibition of the mitochondrial oxidation of fatty acids by tetracycline in mice and in man: possible role in microvesicular steatosis induced by this antibiotic,” Hepatology, vol. 8, no. 5, pp. 1056–1062, 1988.
[118]
D. J. Glenn, F. Wang, M. Nishimoto et al., “A murine model of isolated cardiac steatosis leads to cardiomyopathy,” Hypertension, vol. 57, no. 2, pp. 216–222, 2011.
[119]
G. Petrosillo, M. Matera, N. Moro, F. M. Ruggiero, and G. Paradies, “Mitochondrial complex I dysfunction in rat heart with aging: critical role of reactive oxygen species and cardiolipin,” Free Radical Biology and Medicine, vol. 46, no. 1, pp. 88–94, 2009.
[120]
E. J. Lesnefsky and C. L. Hoppel, “Cardiolipin as an oxidative target in cardiac mitochondria in the aged rat,” Biochimica et Biophysica Acta, vol. 1777, no. 7-8, pp. 1020–1027, 2008.
[121]
H. J. Lee, J. Mayette, S. I. Rapoport, and R. P. Bazinet, “Selective remodeling of cardiolipin fatty acids in the aged rat heart,” Lipids in Health and Disease, vol. 5, article 2, 2006.
[122]
S. Judge, Y. M. Jang, A. Smith, T. Hagen, and C. Leeuwenburgh, “Age-associated increases in oxidative stress and antioxidant enzyme activities in cardiac interfibrillar mitochondria: implications for the mitochondrial theory of aging,” FASEB Journal, vol. 19, no. 3, pp. 419–421, 2005.
[123]
S. W. Fannin, E. J. Lesnefsky, T. J. Slabe, M. O. Hassan, and C. L. Hoppel, “Aging selectively decreases oxidative capacity in rat heart interfibrillar mitochondria,” Archives of Biochemistry and Biophysics, vol. 372, no. 2, pp. 399–407, 1999.
[124]
C. C. Preston, A. S. Oberlin, E. L. Holmuhamedov et al., “Aging-induced alterations in gene transcripts and functional activity of mitochondrial oxidative phosphorylation complexes in the heart,” Mechanisms of Ageing and Development, vol. 129, no. 6, pp. 304–312, 2008.
[125]
J. Marín-García, Y. Pi, and M. J. Goldenthal, “Mitochondrial-nuclear cross-talk in the aging and failing heart,” Cardiovascular Drugs and Therapy, vol. 20, no. 6, pp. 477–491, 2006.
[126]
S. A. Mohamed, T. Hanke, A. W. Erasmi et al., “Mitochondrial DNA deletions and the aging heart,” Experimental Gerontology, vol. 41, no. 5, pp. 508–517, 2006.
[127]
M. R. Meyer, D. J. Clegg, E. R. Prossnitz, and M. Barton, “Obesity, insulin resistance and diabetes: sex differences and role of oestrogen receptors,” Acta Physiologica, vol. 203, no. 1, pp. 259–269, 2011.
[128]
B. Niemann, Y. Chen, M. Teschner, L. Li, R.-E. Silber, and S. Rohrbach, “Obesity induces signs of premature cardiac aging in younger patients: the role of mitochondria,” Journal of the American College of Cardiology, vol. 57, no. 5, pp. 577–585, 2011.
[129]
J. G. Duncan, “Mitochondrial dysfunction in diabetic cardiomyopathy,” Biochimica et Biophysica Acta, vol. 1813, no. 7, pp. 1351–1359, 2011.
[130]
P. J. Oliveira, “Cardiac mitochondrial alterations observed in hyperglycaemic rats—what can we learn from cell biology?” Current Diabetes Reviews, vol. 1, no. 1, pp. 11–21, 2005.
[131]
J. Suski, M. Lebiedzinska, N. G. Machado et al., “Mitochondrial tolerance to drugs and toxic agents in ageing and disease,” Current Drug Targets, vol. 12, no. 6, pp. 827–849, 2011.
[132]
V. A. Sard？o, S. L. Pereira, and P. J. Oliveira, “Drug-induced mitochondrial dysfunction in cardiac and skeletal muscle injury,” Expert Opinion on Drug Safety, vol. 7, no. 2, pp. 129–146, 2008.
[133]
A. Ascens？o, J. Lumini-Oliveira, P. J. Oliveira, and J. Magalh？es, “Mitochondria as a target for exercise-induced cardioprotection,” Current Drug Targets, vol. 12, no. 6, pp. 860–871, 2011.
[134]
J. Lumini-Oliveira, J. Magalh？es, C. V. Pereira, A. C. Moreira, P. J. Oliveira, and A. Ascens？o, “Endurance training reverts heart mitochondrial dysfunction, permeability transition and apoptotic signaling in long-term severe hyperglycemia,” Mitochondrion, vol. 11, no. 1, pp. 54–63, 2011.
[135]
M. L. Johnson, Z. Zarins, J. A. Fattor et al., “Twelve weeks of endurance training increases FFA mobilization and reesterification in postmenopausal women,” Journal of Applied Physiology, vol. 109, no. 6, pp. 1573–1581, 2010.
[136]
Z. A. Zarins, G. A. Wallis, N. Faghihnia et al., “Effects of endurance training on cardiorespiratory fitness and substrate partitioning in postmenopausal women,” Metabolism, vol. 58, no. 9, pp. 1338–1346, 2009.
[137]
A. M. Moustafa and V. Boshra, “The possible role of L-carnitine on the skeletal muscle of ovariectomized rats,” Journal of Molecular Histology, vol. 42, no. 3, pp. 217–225, 2011.
[138]
I. Baeza, J. Fdez-Tresguerres, C. Ariznavarreta, and M. De La Fuente, “Effects of growth hormone, melatonin, oestrogens and phytoestrogens on the oxidized glutathione (GSSG)/reduced glutathione (GSH) ratio and lipid peroxidation in aged ovariectomized rats,” Biogerontology, vol. 11, no. 6, pp. 687–701, 2010.
[139]
R. E. White, R. Gerrity, S. A. Barman, and G. Han, “Estrogen and oxidative stress: a novel mechanism that may increase the risk for cardiovascular disease in women,” Steroids, vol. 75, no. 11, pp. 788–793, 2010.
[140]
J.-F. Arnal, P.-Y. Scarabin, F. Trémollières, H. Laurell, and P. Gourdy, “Estrogens in vascular biology and disease: where do we stand today?” Current Opinion in Lipidology, vol. 18, no. 5, pp. 554–560, 2007.
[141]
T. L. Zern, R. J. Wood, C. Greene et al., “Grape polyphenols exert a cardioprotective effect in pre- and postmenopausal women by lowering plasma lipids and reducing oxidative stress,” Journal of Nutrition, vol. 135, no. 8, pp. 1911–1917, 2005.
[142]
M. Sun, F. Qian, W. Shen, et al., “Mitochondrial nutrients stimulate performance and mitochondrial biogenesis in exhaustively exercised rats,” Scandinavian Journal of Medicine and Science in Sports. In press.
[143]
A. Biala, E. Tauriainen, A. Siltanen et al., “Resveratrol induces mitochondrial biogenesis and ameliorates Ang II-induced cardiac remodeling in transgenic rats harboring human renin and angiotensinogen genes,” Blood Pressure, vol. 19, no. 3, pp. 196–205, 2010.
[144]
G. Szabó, “A glass of red wine to improve mitochondrial biogenesis? Novel mechanisms of resveratrol,” American Journal of Physiology: Heart and Circulatory Physiology, vol. 297, no. 1, pp. H8–H9, 2009.
