Regulation of Amino Acid and Glucose Transporters in Endothelial and Smooth Muscle Cells

Abstract

While transport processes for amino acids and glucose have long been known to be expressed in the luminal and abluminal membranes of the endothelium comprising the blood-brain and blood-retinal barriers, it is only within the last decades that endothelial and smooth muscle cells derived from peripheral vascular beds have been recognized to rapidly transport and metabolize these nutrients. This review focuses principally on the mechanisms regulating amino acid and glucose transporters in vascular endothelial cells, although we also summarize recent advances in the understanding of the mechanisms controlling membrane transport activity and expression in vascular smooth muscle cells. We compare the specificity, ionic dependence, and kinetic properties of amino acid and glucose transport systems identified in endothelial cells derived from cerebral, retinal, and peripheral vascular beds and review the regulation of transport by vasoactive agonists, nitric oxide (NO), substrate deprivation, hypoxia, hyperglycemia, diabetes, insulin, steroid hormones, and development. In view of the importance of NO as a modulator of vascular tone under basal conditions and in disease and chronic inflammation, we critically review the evidence that transport of L-arginine and glucose in endothelial and smooth muscle cells is modulated by bacterial endotoxin, proinflammatory cytokines, and atherogenic lipids. The recent colocalization of the cationic amino acid transporter CAT-1 (system y(+)), nitric oxide synthase (eNOS), and caveolin-1 in endothelial plasmalemmal caveolae provides a novel mechanism for the regulation of NO production by L-arginine delivery and circulating hormones such insulin and 17beta-estradiol.

Characterisation of glucose transporters in the intact coronary artery endothelium in rats: GLUT-2 upregulated by long-term hyperglycaemia

“…Consistent with previous studies [6], we found GLUT-1 in endothelial cells. We also found that it is asymmetrically distributed, with a greater abundance on the abluminal side.…”

“…Most studies have focused on the mechanism by which elevated intracellular glucose induces endothelial dysfunction [4,5]. It is only recently that the regulation of glucose transport in endothelial cells has been examined [6], and most of this work has been on the blood-brain and blood-retina barriers [7,8,9]. The integrity of endothelial cells of small contractile vessels is also affected by hyperglycaemia, and the coronary arteries are among the most susceptible to atheroma, but few studies have directly examined glucose transporters in these vessels [6].…”

“…It is only recently that the regulation of glucose transport in endothelial cells has been examined [6], and most of this work has been on the blood-brain and blood-retina barriers [7,8,9]. The integrity of endothelial cells of small contractile vessels is also affected by hyperglycaemia, and the coronary arteries are among the most susceptible to atheroma, but few studies have directly examined glucose transporters in these vessels [6]. Despite having the same embryonic origin, there is a strong heterogeneity between endothelial cells of different vascular beds, and even those within the same vascular bed are known to have morphological, physiological and biochemical differences [10,11].…”

Insights into human hypertension: the role of endothelial dysfunction

“…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.…”

“…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.…”