Aging-Shifted Prostaglandin Profile in Endothelium as a Factor in Cardiovascular Disorders

Age-associated endothelium dysfunction is a major risk factor for the development of cardiovascular diseases. Endothelium-synthesized prostaglandins and thromboxane are local hormones, which mediate vasodilation and vasoconstriction and critically maintain vascular homeostasis. Accumulating evidence indicates that the age-related changes in endothelial eicosanoids contribute to decline in endothelium function and are associated with pathological dysfunction. In this review we summarize currently available information on aging-shifted prostaglandin profiles in endothelium and how these shifts are associated with cardiovascular disorders, providing one molecular mechanism of age-associated endothelium dysfunction and cardiovascular diseases. 1. Introduction Cardiovascular disorders, including atherosclerosis, coronary artery disease, heart failure, and hypertension, remain the leading cause of death worldwide [1]. These diseases are among several pathological conditions that are associated with aging [2–4], and age is a primary risk factor for their development [5, 6]. Endothelium is a thin layer of epithelial cells which line the interior of lymph and blood vessels and is a major component of the vascular wall. One important contributor to the development of cardiovascular diseases is a dysfunctional endothelium. Endothelial dysfunction is considered a fair predictor of cardiovascular diseases [4, 7–11]. Furchgott and Zawadzki unequivocally demonstrated that the endothelium is required for normal vessel relaxation [12]. Besides inducing relaxation, normal and healthy endothelium regulates vessel wall permeability, blood flow, vascular tone, and structure and exerts anticoagulant and fibrinolytic properties [13]. Aging adversely affects these normal functions of the endothelium, enhancing vasospasm and thrombosis, leading to eventual cardiovascular diseases [4, 14–16]. Age-impaired vascular relaxation has been shown in different human vascular beds including brachial artery, aorta, coronary artery, carotid, and mesenteric microvessels [14–21]. In line with these reports, additional evidence has been obtained in different vascular beds of animals including dogs [2, 22], rats [2, 23–32] and mice [33, 34]. This reduced relaxation is accompanied with increased blood pressure [35–39]. Elevated blood pressure is an important cardiovascular risk factor that can eventually lead to heart failure. Normal endothelial function is regulated by a controlled balance between endothelium-dependent relaxing factors and endothelium-dependent contracting factors. The main