Research Article: Recent Progress in Vascular Aging: Mechanisms and Its Role in Age-related Diseases

Date Published: July 21, 2017

Publisher: JKL International LLC

Author(s): Xianglai Xu, Brian Wang, Changhong Ren, Jiangnan Hu, David A. Greenberg, Tianxiang Chen, Liping Xie, Kunlin Jin.

http://doi.org/10.14336/AD.2017.0507

Abstract

As with many age-related diseases including vascular dysfunction, age is considered an independent and crucial risk factor. Complicated alterations of structure and function in the vasculature are linked with aging hence, understanding the underlying mechanisms of age-induced vascular pathophysiological changes holds possibilities for developing clinical diagnostic methods and new therapeutic strategies. Here, we discuss the underlying molecular mediators that could be involved in vascular aging, e.g., the renin-angiotensin system and pro-inflammatory factors, metalloproteinases, calpain-1, monocyte chemoattractant protein-1 (MCP-1) and TGFβ-1 as well as the potential roles of testosterone and estrogen. We then relate all of these to clinical manifestations such as vascular dementia and stroke in addition to reviewing the existing clinical measurements and potential interventions for age-related vascular dysfunction.

Partial Text

Among aging-related diseases, age-specific mortality rates from cardiovascular diseases (CVDs) rise exponentially from more than 40% of all deaths at age 65-74 to almost 60% in the 85 and over age group to become the leading cause of death [1]. The Global Burden of Disease Study reported that 15.6 million people died from CVDs worldwide in 2010, accounting for 29.6% of all deaths, or twice as many as the deaths from cancers [2]. This proportion is even higher in Europe, where CVDs are responsible for nearly half of all deaths [3]. Cerebrovascular diseases, if considered separately, accounts for 12% of all deaths in Europe annually. Moreover, cerebrovascular diseases such as vascular cognitive impairment dramatically decrease the quality of life, even though they do not cause death directly. Therefore, aging research is of great importance, especially in the context of cerebrovascular diseases, from bench to bedside. Understanding the mechanisms underlying age-induced vascular pathophysiological alterations also holds possibilities for developing clinical diagnostic methods and new therapeutic strategies.

Blood pressure changes with advancing age. There is a linear rise in systolic blood pressure induced by arterial stiffness and a concurrent increase in diastolic blood pressure due to endothelial dysfunction-induced high peripheral vascular resistance until about the age of 50 [138]. Thereafter, high systolic blood pressure accelerates arterial stiffness, perpetuating a vicious cycle. In older individuals, increased arterial stiffness decreases diastolic blood pressure while systolic blood pressure keeps rising, which forms an age-related systolic-diastolic blood pressure divergence, resulting in a widen pulse pressure. Even in older normotensives, they have higher arterial stiffness, systolic blood pressure and pulse pressure vs. the young [139]. Increasing pulse pressure or hypertension increases cardiac afterload, then leads to left ventricular hypertrophy. In the brain, increased pulse pressure penetrates further into cerebral microcirculation, which may potentially expose capillaries to damaging levels of elevated pressure pulsatility. Thus, cerebral microvascular remodeling and dysfunction increase vascular resistance in response to elevated pulse pressure and limit the penetration of excessive pulsatility directly into the capillaries [140]. However, cerebral microvascular remodeling and dysfunction increases minimal resistance and reduces vasodilatory reserve. Accompanying age-related microvessel loss, these lead to an increased susceptibility to hypoperfusion and reduce the efficiency of oxygen and energy delivery, which can promote cerebral microvascular disease [141, 142] and cognitive impairment [143, 144].

The molecular targets through which aging perturbs vascular homeostasis are manifold and appear to include increased expression or activation of TNF-α, IL-1β, IL-6 family members and CRP, which promote inflammation and endothelial dysfunction. Currently, there are many non-invasive ways to examine vascular aging through arterial stiffness and endothelial function assessments. New interventions such as the use of statins and RAS drugs to treat vascular aging have been suggested, but clinicians and patients should consider potential adverse effects.

 

Source:

http://doi.org/10.14336/AD.2017.0507

 

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