Insights into human hypertension: the role of endothelial dysfunction

Abstract

Atherosclerosis is considered an ubiquitous pathological process. In patients symptomatic for coronary artery or carotid or peripheral arterial disease, other localizations -still asymptomatic -of atherosclerotic lesions are often found. Despite this consideration, the patterns of arteries developing atherosclerosis can be quite diverse: for example, lesions prevalently develop in regions where the flow is either low or turbulent such as where artery bifurcates, mammalian artery are nearly unaffected by atherosclerosis. 1 So, what makes the difference? The answer probably lies in the marked phenotypic variation between endothelial cells in the different vascular locations, and in the different responses of the vascular layers to the same stimulus in the same individual, as well.Indeed, the vascular endothelium, once believed to be an inert edge between artery and blood, is now recognized as an organ per se. 2 Many studies over the past 10 years indicate that endothelial cells have important transport functions, act as the provision of an antithrombogenic interface, control of platelet adherence and thrombosis, as well as active actions in inflammation and vascular tone. Indeed, use of simple drugs such as aspirin may influence endothelial function in hypertension. 3,4 Endothelial cells also facilitate the transport of glucose by GLUT, 5 mainly present in brain barrier, of amino acids (such as L-arginine, a substrate for nitric oxide (NO)). Recent data even suggest a relationship of the endothelium to angiogenesis. 6 In addition, hypertensive patients with diabetes mellitus have endothelial dysfunction that can be related to urinary albumin excretion and inflammation, as well as modified by antihypertensive therapy. [7][8][9] Of note, endothelial cells may be actively involved in inflammation through the expression of Toll-like receptors -4 and -2, leading to increased expression of inflammation mediators such as chemokines, adhesion molecules and metalloproteinase. 10 Finally, endothelial cells are also intimately involved in haemostasis and coagulation by the production of substances such as tissue factor pathway inhibitor, thrombomodulin, endothelial protein C receptor and von Willebrand factor. 5 Of particular interest, in the pathophysiology of the endothelium, is the endothelial regulation of vascular tone. 2 Endothelial cells produce several vasoactive substances, and among them is NO, the most powerful vasodilator. 2 NO is produced by endothelial cells via NOS III (eNOS) or via NOS II (iNOSII), where the former is constitutive and acts to maintain the vascular musculature in a state of vasodilatation, while the latter is inducible by immunological stimuli. 2,11 Indeed, several studies have demonstrated that low NO, whose circulating levels are considered as a surrogate of endothelial dysfunction, is an early marker in patients with common cardiovascular risk factors, such as diabetes, smoking and hypertension. 2 In a recent issue of the Journal of Human Hypertension, Srivastava et al. 12 confirm that in p...

Statins and hypertension

“…13 Endothelial dysfunction is associated with hypertension and strongly with other cardiovascular risk factors including existing atherosclerosis, diabetes mellitus, inflammation and LDL-C. [14][15][16][17][18][19] Nitrates act as vasodilators and lower blood pressure acutely through an endothelium-independent mechanism by supplying excess nitric oxide to the vascular wall. 20,21 This would imply that any agent capable of improving endothelial dysfunction should be associated with a reduction in blood pressure.…”

Antioxidant protection: yet another function of endothelial progenitor cells?

“…Indeed, the endothelium is believed to play a pivotal role in many cardiovascular disease states, including hypertension. 3 However, the concept of 'endothelial dysfunction' should not be limited purely to endothelial abnormalities, but should include consideration of a host of anomalies that occur in the conduit vessel wall, within the blood and perhaps even extended to alterations in the number and/or function of endothelial progenitor cells (EPCs) within the bone marrow.…”

“…Some have speculated that endothelial NO activity is the hallmark of endothelial function, and the release of NO plays a critical role in the control of vascular tone. 3 Potent antiaggregatory and proangiogenic properties of NO are also well determined. The clinical implications of endothelial dysfunction and the association between reduced NO bioavailability, cardiovascular risk factors (including hypertension) and cardiac events is well established.…”

“…Although EPCs are generally considered immature cells, it is increasingly apparent that they may rapidly accumulate features of maturityeven before their fusion into the vascular endothelium. Indeed, reduced extracellular SOD activity is closely associated with increased vascular oxidative stress and contributes to endothelial dysfunction in patients with hypertension, 3 congestive heart failure 24 and coronary artery disease. 25 Given the high vulnerability of the mature endothelial cells to oxidative stress -even in the conditions of the chronic cardiovascular pathologyhow do EPCs survive and maintain their regenerative properties in the 'aggressive' environment of ischemic tissue?…”

Endothelial progenitor cells in the vascular pathophysiology of hypertension: arterial stiffness, ageing and more

“…von Willebrand factor) is less clear. 4,5 Furthermore, the mechanisms for the observed endothelial dysfunction are poorly understood at present. 6 With advancing age, there is progressive thickening of arterial walls -predominantly in the intimal layer -with marked increases in the intimal to medial thickness ratio.…”