Wall Remodeling During Luminal Expansion of Mesenteric Arterial Collaterals in the Rat

Abstract

Wall remodeling associated with rapid luminal enlargement of collateral mesenteric arteries in rats was investigated 1 and 4 weeks after creation of a collateral pathway by ligating three to four sequential arteries. Paired observations were made of inner diameters of collateral and normal arteries in the same animals. Arterial blood flow was measured at the final observation. Sections of arteries were processed for morphological measurements. After 4 weeks, inner arterial diameter was increased more at the beginning (63 +/- 6%) than the end (25 +/- 9%) of the collateral pathway. At 1 and 4 weeks, respectively, cross-sectional areas of collateral relative to normal arteries were increased by 46 +/- 5% and 59 +/- 13% (lumen), 55 +/- 8% and 65 +/- 14% (media), and 89 +/- 18% and 60 +/- 31% (intima). The wall expansion during luminal enlargement resulted in a normal medial thickness:luminal radius relationship. At 1 week postligation, wall shear rate remained elevated and endothelial but not smooth muscle hyperplasia had occurred (intimal nuclei: 40 +/- 1.7 collateral versus 24 +/- 3.0 normal; medial nuclei: 42 +/- 6.8 collateral versus 37 +/- 2.1 normal). At 4 weeks, wall shear rate in collaterals was similar to normal arteries, and smooth muscle hyperplasia had taken place (medial nuclei: 84 +/- 9.4 collateral versus 44 +/- 4.7 normal). The data demonstrate that wall expansion associated with rapid luminal enlargement of these collaterals involves hyperplasia of both endothelial and smooth muscle cells; however, smooth muscle proliferation does not occur until after wall shear rate is reduced. The specific cellular adaptations that occur during collateral development may depend on the level of wall shear and shear-dependent modulation of endothelial growth factors.

Altered Flow–Induced Arterial Remodeling in Vimentin-Deficient Mice

“…24 In various previous experimental settings, chronic flow increases and flow decreases have been reported to result in outward and inward arterial remodeling, respectively. 3,4,8,10,13,17 The structural diameter changes were observed to lead to a normalization of wall shear stress and to be accompanied by a compensatory change in medial mass, which restores circumferential wall stress. Changes in arterial smooth muscle cell size and number have been suggested to participate in these compensatory or adaptive forms of arterial remodeling in response to altered BF.…”

“…[1][2][3][4][5][6][7][8] Arterial structural responses to changes in shear stress operate during physiological adaptations to postnatal development, 9,10 exercise, 11 and pregnancy 12 and in pathological conditions, such as arteriovenous shunting 13 and arterial occlusive disease. 14,15 They have been suggested to be endothelium dependent 16 and to display similarities to acute shear-induced vasodilatation in response to an increase in arterial blood flow (BF).…”

DNA Methyltransferase 1–Dependent DNA Hypermethylation Constrains Arteriogenesis by Augmenting Shear Stress Set Point

“…The concept of an arterial homeostatic wall shear stress magnitude (ie, shear stress set point) at which vessels maintain a steady‐state luminal diameter72 arises from Murray's principle of minimum work 73. Outward collateral artery growth is therefore hypothesized to stop once normalization to the shear stress set point has been achieved 2, 3, 4, 5. Premature normalization to the shear stress set point has been a predominant rationalization for the failure of collateral arteries to realize full arteriogenic capacity, frequently reaching only 30% to 40% of the maximal conductance 74.…”

“…The resulting increase in shear stress acting on the endothelium initiates a highly coordinated signaling cascade, ultimately resulting in the outward growth of the collateral vessel 1, 2. Outward luminal growth is hypothesized to continue until normalization to the original shear stress level (ie, the shear stress “set point”) has been achieved 2, 3, 4, 5…”

Time Course of Vascular Structural Changes During and After Short-Term Antihypertensive Treatment

“…For example, regression of medial thickness may result from the reduction in the levels of angiotensin II or the decrease in wall stress, whereas the widening of the lumen may have resulted from the increase in blood flow associated with the increase in arterial pressure following cessation of therapy. [37][38][39] An additional objective was to determine whether the depressor response or the removal of a trophic factor was the critical component in producing persistent changes in MAP and vascular structure. Two groups of SHR received the same degree of ACE inhibition and therefore a similar reduction in the trophic factor angiotensin II, with one group receiving a diet that was low in sodium.…”