Elastin Haploinsufficiency Induces Alternative Aging Processes in the Aorta

Abstract

Elastin, the main component of elastic fibers, is synthesized only in early life and provides the blood vessels with their elastic properties. With aging, elastin is progressively degraded, leading to arterial enlargement, stiffening, and dysfunction. Also, elastin is a key regulator of vascular smooth muscle cell proliferation and migration during development since heterozygous mutations in its gene (Eln) are responsible for a severe obstructive vascular disease, supravalvular aortic stenosis, isolated or associated to Williams syndrome. Here, we have studied whether early elastin synthesis could also influence the aging processes, by comparing the structure and function of ascending aorta from 6-and 24-month-old Eln+/− and Eln+/+ mice. Eln+/− animals have high blood pressure and arteries with smaller diameters and more rigid walls containing additional

Nonmuscle Myosin Light Chain Kinase: A Key Player in Intermittent Hypoxia‐Induced Vascular Alterations

“…Vessels were carefully cleaned of adipose tissue, cannulated, and mounted onto a pressure arteriograph, placed onto a microscope with video monitoring. Mechanistic study was performed, as previously described 26, 27, 28. Circumferential wall stress (representative of all forces that are circumferentially applied on each small portion of the vessel wall) and incremental elastic modulus (Einc) (representative of wall stiffness) were calculated from the inner and outer diameters at transluminal pressures ranging from 0 to 175 mm Hg, according to the formulas given by Gibbons and Shadwick 29…”

“…Responses to PE are presented as the percentage decrease in inner diameter (ID), compared with the control diameter at 75 mm Hg before PE application: PE‐induced contraction (%)=100×(ID control −ID PE )/ID control . Responses to Ach are presented as the percentage restoration of the ID after PE‐induced constriction: Ach‐induced vasodilation (%)=100×(ID Ach+PE −ID PE )/(ID control −ID PE ) 27, 28…”

The genomic basis of the Williams – Beuren syndrome

“…The elastin gene is the best-explored gene of the WBS region and it has been demonstrated that haploinsufficiency as well as heterozygous point mutations cause SVAS [29 -34, 170]. Heterozygous knock out mice of the Eln gene display high blood pressure, constriction of arteries and rigid arterial walls [170].…”

Mechanisms and treatment of cardiovascular disease in Williams-Beuren syndrome

“…Interestingly, Eln +/-mice are protected from vascular remodeling following carotid artery ligation in the ipsilateral vessel while enhanced remodeling occurs in the contralateral artery (88), suggesting that elastin haploinsufficiency may differentially affect ligation-mediated and flow-mediated injury responses. Eln +/-mice show the same CV remodeling response in the renal artery clipping model of adult hypertension as do wild-type animals (89) but are protected from the age-related vessel wall thickening observed in wild-type animals (90). Further clinical studies are needed to determine whether patients with WBS are also protected from age-related vascular changes.…”