Toward functional genomics of flow-induced outward remodeling of resistance arteries

Abstract

.-In resistance-sized arteries, a chronic increase in blood flow leads to increases in arterial structural luminal diameter and arterial wall mass. In this review, we summarize recent evidence that outward remodeling of resistance arteries 1) can help maintain and restore tissue perfusion, 2) is not intimately related to flowinduced vasodilatation, 3) involves transient dedifferentiation and turnover of arterial smooth muscle cells, and 4) is preceded by increased expression of matricellular proteins, which have been shown to promote disassembly of focal adhesion sites. Studies of experimental and physiological resistance artery remodeling involving differential gene expression analyses and the use of knockout and transgenic mouse models can help unravel the mechanisms of outward remodeling.flow-induced vasodilatation; matricellular protein; gene expression microarray analysis IN ARTERIES, TRANSMURAL PRESSURE and blood flow influence wall thickness and structural luminal diameter (13,16,28,29,49). Mathematical modeling, cell and molecular biological approaches, and experiments in genetically modified animals are beginning to shed light on the mechanisms that underlie these arterial remodeling responses. Here, we summarize recent observations concerning flow-induced outward remodeling of resistance arteries. Exploration of this type of arterial structural response might lead to pharmacological treatments to 1) improve collateral perfusion and 2) reverse the inward arterial remodeling in essential hypertension. TERMINOLOGYRemodeling is frequently used to describe any alteration of arterial structure. In agreement with others (4, 38), we find it useful to note the differences among several types of arterial remodeling: 1) neointima formation, 2) alteration of the arterial structural luminal diameter (outward or inward), and 3) alteration of tunica media mass (hypertrophic, eutrophic, and hypotrophic). Although this classification is helpful, it also highlights gaps in current knowledge, such as the manner in which media, adventitia, and ultrastructural wall components, such as extracellular matrix, focal adhesion sites, and cytoskeleton, determine the diameter. Arterial structural diameter refers to the maximally dilated diameter and results from the elastic properties of the arterial wall. The diameter of an arterial segment in vivo obviously depends on this structural diameter and on the degree of vasomotor tone or smooth muscle contractile activity.Resistance arteries are small (300 -100 m diameter) muscular arteries that are situated between large elastic conduit arteries and arterioles. In contrast to the large arteries, resistance arteries 1) not only respond to, but also influence, local mean arterial pressure and blood flow, 2) rarely, if ever, develop a neointima, and 3) do not display hypertrophy but, rather, exhibit inward eutrophic remodeling during chronic hypertension (37). In resistance arteries, circumferential wall stress and wall shear stress are maintained at higher values than in arterioles (43)...

Induction of Endothelial Nitric Oxide Synthase Expression by IL-17 in Human Vascular Endothelial Cells: Implications for Vascular Remodeling in Transplant Vasculopathy

“…Thickening of the arterial intima in TV is caused by immunemediated damage and dysfunction of the graft endothelium, which leads to leukocyte and smooth muscle cell migration into this layer of the vessel wall (15). Wall thickening due to intimal hyperplasia is opposed by outward remodeling, a process that is believed to involve the acute production of endothelial-derived vasodilators, such as NO, followed by chronic changes that involve extracellular matrix alterations (16). The resultant arterial outward expansion preserves lumen size and blood flow (17).…”

Role of Angiotensin II in the Remodeling Induced by a Chronic Increase in Flow in Rat Mesenteric Resistance Arteries

“…[5][6][7] Chronic changes in blood flow occur in physiological conditions, such as exercise, pregnancy, or postnatal development, and in pathological conditions, such as arterial occlusive diseases, diabetes mellitus, or hypertension. 1,8 A chronic increase in blood flow induces remodeling of the vascular wall to adapt arterial wall strain to the new hemodynamic conditions, as described in large blood vessels 9 and in small resistance arteries. 1,8 Indeed, in resistance arteries, a chronic increase in blood flow induces an increase in diameter associated with media thickening (hypertrophic remodeling).…”

“…1,8 A chronic increase in blood flow induces remodeling of the vascular wall to adapt arterial wall strain to the new hemodynamic conditions, as described in large blood vessels 9 and in small resistance arteries. 1,8 Indeed, in resistance arteries, a chronic increase in blood flow induces an increase in diameter associated with media thickening (hypertrophic remodeling). 10 -12 The mechanism involved in the rise in diameter is well described in large conductance arteries.…”

Involvement of angiotensin II in the remodeling induced by a chronic decrease in blood flow in rat mesenteric resistance arteries

“…4,5,6 Chronic changes in blood flow occur in physiological conditions such as exercise, pregnancy and postnatal development, as well as in pathological conditions such as arterial occlusive diseases, diabetes and hypertension. 7,8 These changes in flow induce remodeling of the vascular wall to adapt arterial wall strain to the new hemodynamic conditions, as described in large 9 and small (resistance) arteries. 7,8 In large arteries, a chronic reduction in blood flow induces inward remodeling associated with intimal invasion.…”

“…7,8 These changes in flow induce remodeling of the vascular wall to adapt arterial wall strain to the new hemodynamic conditions, as described in large 9 and small (resistance) arteries. 7,8 In large arteries, a chronic reduction in blood flow induces inward remodeling associated with intimal invasion. 9 In small resistance arteries (RAs), a chronic reduction in blood flow induces inward remodeling without intimal invasion.…”