Abstract
Vascular aging is associated with structural and functional modifications of the arteries, and by an increase in arterial wall thickening in the intima and the media, mainly resulting from structural modifications of the extracellular matrix (ECM) components. Among the factors known to accumulate with aging, advanced lipid peroxidation end products (ALEs) are a hallmark of oxidative stress-associated diseases such as atherosclerosis. Aldehydes generated from the peroxidation of polyunsaturated fatty acids (PUFA), (4-hydroxynonenal, malondialdehyde, acrolein), form adducts on cellular proteins, leading to a progressive protein dysfunction with consequences in the pathophysiology of vascular aging. The contribution of these aldehydes to ECM modification is not known. This study was carried out to investigate whether aldehyde-adducts are detected in the intima and media in human aorta, whether their level is increased in vascular aging, and whether elastin fibers are a target of aldehyde-adduct formation. Immunohistological and confocal immunofluorescence studies indicate that 4-HNE-histidine-adducts accumulate in an age-related manner in the intima, media and adventitia layers of human aortas, and are mainly expressed in smooth muscle cells. In contrast, even if the structure of elastin fiber is strongly altered in the aged vessels, our results show that elastin is not or very poorly modified by 4-HNE. These data indicate a complex role for lipid peroxidation and in particular for 4-HNE in elastin homeostasis, in the vascular wall remodeling during aging and atherosclerosis development.
Highlights
Aging is the largest known risk factor for most human diseases [1,2,3,4]
The aim of this study was to check whether age-related elastin modifications observed in human aortas are correlated with an increased accumulation of HNE-adducts, and whether elastin is modified by 4-HNE in human vessels
Our results indicate that HNE-adducts accumulate in human aorta in an age-related manner, mainly in the intima and the adventitia, and at a lesser extent in the media. 4-HNE-adducts are mainly cellular, and are not detected on elastin, even in elderly, indicating that elastin is not a target of advanced lipid peroxidation end products (ALEs) in the vascular wall
Summary
The aging process generates a progressive loss of biological functions and abilities to manage metabolic changes, with particular impact on the development of cardiovascular diseases [5,6], which represent the major cause of morbidity and mortality in aged people [7,8]. Two major scaffolding ECM proteins provide structural integrity and elasticity to the vessels, allowing them to stretch while retaining their ability to return to their original shape when the pressure is over. Vascular aging is most of the time associated with structural and functional modifications of the arteries, even in healthy elderly, and by an increase in arterial wall thickening in the intima and the media, mainly resulting from the accumulation and structural modification of ECM components and a disorganization of SMC [10,11]. Increased collagen deposition and reduction of elastin content due to elastin fiber degradation, often associated with vascular calcifications, contribute
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