Concept of Extremes in Vascular Aging

Abstract

With advancing age, changes in the arterial wall contribute to what has been called vascular aging, and in some prematurely affected subjects even early vascular aging (EVA).[[1], [2], [3], [4], [5]] Several years ago,[1] we listed various components of EVA, including arteriosclerosis, atherosclerosis, and excess vasoconstriction, with their clinical expression: arterial stiffening and increased central pulse pressure, carotid intima media thickening and endothelial dysfunction, and increased total peripheral resistance, respectively. However, an average vascular aging may not be the desirable goal for patients and their physicians in a population where cardiovascular risk factors are prevalent, and an ideal aging[8] or at least a healthy vascular aging (HVA)[38],[39] would be preferable. The boundaries between early vascular aging (EVA), average vascular aging, healthy vascular aging (HVA), and supernormal vascular aging (SUPERNOVA) are presented as gray zones (Text). Thus, vascular aging based on cardiovascular risk factor may fail at identifying people excessively sensitive (EVA) to or protected against (HVA) risk factors, whereas PWV represents the cumulative damage of all cardiovascular risk factors on the arterial wall. The glucagon-like peptide-1 analog exendin-4 may also contribute to the redox homeostasis by reducing the nucleocytoplasmic shuttling of Nrf2 through its acetylation, thus increasing its transcriptional activity and decreasing VSMC senescence.[68] Localized disturbed blood flow has emerged as a master regulator of the association of Nrf2 with HDAC1/2/3 leading to deacetylation of Nrf2 and sensitizing the endothelium to oxidative stress.[69] Additional potential mechanisms holding off vascular aging and VSMC senescence in NMRs include increased levels of high molecular mass hyaluronan and differentially expressed long noncoding RNAs among which several are coexpressed with HA-related genes.[70].