Impaired collateral development in mature rats

Abstract

The effect of maturation on collateral development of resistance arteries was investigated. Three to four sequential mesenteric arteries were ligated to create collateral pathways in anesthetized young (ϳ200 g) and mature (ϳ600 g) rats. Blood flow was similarly elevated in collaterals of young and mature animals. In vivo inner arterial diameter was increased only within young collaterals (33 Ϯ 7%, P Ͻ 0.001). Increases in number of intimal nuclei (57 Ϯ 10% vs. 52 Ϯ 14%) and cross-sectional medial area (33 Ϯ 13% vs. 38 Ϯ 5%) were similar between young and mature collaterals. Relative to the same animal controls, collateral endothelial nitric oxide synthase mRNA was increased as much in mature as in young rats. Proteomic analysis revealed significant differences in protein expression with maturation between control arteries as well as flow-loaded collateral vessels. The results indicate that, whereas intimal and medial remodeling events were similar in collaterals of young and mature rats, luminal expansion occurred only in young rats. Alteration in arterial protein expression with maturation and altered responses to stimuli for collateral development may contribute to this impairment. luminal expansion; resistance artery; proteomic analysis; eNOS; arterial remodeling DURING THE MATURATION OF PHYSIOLOGICAL SYSTEMS, many of the mechanisms governing various functional outcomes are altered. With increasing age, these alterations may in turn lead to functional impairments and exacerbate disease. The vascular system has been shown to follow this path with regard to a variety of functions, including blood vessel reactivity (20, 35) and vascular growth and remodeling (3,24,27). Studies from our laboratory have focused on understanding processes involved in collateral artery remodeling after chronic elevation of blood flow. Currently, little is known about how maturation and aging affect the capacity for collateral development. The clinical observation/experience is that collateral growth (32) and flow-induced luminal enlargement of arteries (8) occur in adult humans. However, flow-mediated remodeling in large conduit arteries, which has many mechanistic similarities to collateral/resistance artery remodeling, has been observed to be impaired with maturation (3, 24).Arterial remodeling occurs after chronic elevation of blood flow and is a complex process involving flow/ shear stimulus transduction and endothelial activation (5, 26). After transduction and activation, remodeling of the entire arterial wall is accomplished through changes in protein expression/activity and cell growth. Luminal dimensions are altered to normalize wall shear stress (3,24,40,46). Age-dependent alterations in any of the mechanisms involved in flow-induced arterial remodeling could influence the capacity for luminal adjustment in response to altered shear. The primary purpose of the current study was to determine whether flow-induced expansion of resistance arteries forming collateral pathways is impaired with maturation and to provide insight r...

Role of the cytoskeleton in flow (shear stress)-induced dilation and remodeling in resistance arteries

“…Superoxides and NO are also able to activate HSPs production 87 and both are produced by endothelial cells in response to shear stress 47 . Enolase, which has properties similar to those of HSPs, is also increased in mesenteric resistance arteries submitted to high flow in young and mature rats 81 . In young rats diameter and medial mass increased whereas in mature rats medial hypertrophy occurred without increase in diameter 81 .…”

“…Interestingly, in mature rats (8-10 month-old) vimentin content was lower than in young animals and no diameter expansion occurred after a chronicle increase in blood flow 81 . In high flow resistance arteries several heat shock proteins (HSP) expression level increased as well, which is a characteristic of a response to a stress 81 . HSPs may be involved in the stabilization of cytoskeletal element after diameter expansion 82 .…”

“…In addition, a proteomic analysis performed in mesenteric resistance submitted chronically to high blood flow for one week shows a significant increase in vimentin content 81 . Interestingly, in mature rats (8-10 month-old) vimentin content was lower than in young animals and no diameter expansion occurred after a chronicle increase in blood flow 81 . In high flow resistance arteries several heat shock proteins (HSP) expression level increased as well, which is a characteristic of a response to a stress 81 .…”

“…HSPs may be involved in the stabilization of cytoskeletal element after diameter expansion 82 . High flow-induced remodeling is also associated with eNOS overexpression and depends on NO production in resistance arteries 74,81 . In addition, in large blood vessels 76 and most probably in resistance arteries (preliminary result: 83 ), high flow-induced remodeling requires a rise in reactive oxygen species (ROS) production.…”

Impact of 2‐Weeks Continuous Increase in Retrograde Shear Stress on Brachial Artery Vasomotor Function in Young and Older Men

“…These changes may contribute to chronically elevated levels of retrograde shear stress with older age,24, 25 and may also impact upon the ability of the vasculature to respond to changes in retrograde shear. Interestingly, previous studies in animals reported distinct adaptations to shear stress between young and older individuals 26, 27, 28, 29. However, no previous study has explored whether prolonged exposure to elevated retrograde shear leads to distinct adaptations in brachial artery vasomotor function between healthy young and older humans.…”