Age‐Associated Changes in the Vascular Renin‐Angiotensin System in Mice

Abstract

Background. This study evaluated whether the change in the renin-angiotensin system (RAS) is associated with arterial aging in mice. Methods. Histologic changes and expressions of transforming growth factor-β (TGF-β), collagen IV, fibronectin, angiotensin II (Ang II), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), prorenin receptor (PRR), Mas receptor (MasR), endothelial nitric oxide synthase (eNOS), NADPH oxidase 2 and oxidase 4 (Nox2 and Nox4), 8-hydroxy-2′-deoxyguanosine (8-OHdG), 3-nitrotyrosine, and superoxide dismutase 1 and dismutase 2 (SOD1 and SOD2) were measured in the thoracic aortas from 2-month-old, 12-month-old, and 24-month-old C57/BL6 mice. Results. Twenty-four-month-old mice showed significantly increased aortic media thickness and expressions of TGF-β, collagen IV, and fibronectin, compared to 2-month-old and 12-month-old mice. The expressions of PRR, ACE, and Ang II, and AT1R-positive area significantly increased, whereas expressions of ACE2 and MasR and AT2R-positive area decreased with age. The expressions of phosphorylated serine1177-eNOS, SOD1, and SOD2 decreased, and the 8-OHdG-positive area and the 3-nitrotyrosine-positive area increased with age. The expression of Nox2 significantly increased with age, but that of Nox4 did not change. Conclusions. The enhanced PRR-ACE-Ang II-AT1R axis and reduced ACE2-MasR axis were associated with arterial aging in mice.

COVID-19 in children and altered inflammatory responses

“…9 Decreasing ACE2 is notable in animal models of ageing. 10 Sodhi et al demonstrated that neutrophil inflammation following bacterial pneumonia was altered by pulmonary ACE2 activity. Alterations in ACE2 are critical for neutrophil influx and lung inflammation.…”

Cardiac changes associated with vascular aging

“…With renal aging, there is an elevated activation of the vascular renin‐angiotensin‐aldosterone‐system (RAAS), leading to increased levels of angiotensin II in the arterial wall. The downstream effect of RAAS activation is the upregulation of tumor growth factor‐beta (TGF‐β), which subsequently increases collagen production and deposition into ECM, resulting in vascular thickening . Furthermore, oxidative stress also upregulates matrix metalloproteinase development and further increases vascular fibrosis leading to LV remodeling and subsequent deleterious CV aging .…”

“…The downstream effect of RAAS activation is the upregulation of tumor growth factorbeta (TGF-β), which subsequently increases collagen production and deposition into ECM, resulting in vascular thickening. 39 Furthermore, oxidative stress also upregulates matrix metalloproteinase development and further increases vascular fibrosis leading to LV remodeling and subsequent deleterious CV aging. 40,41 Table 1 summarizes the common age-associated changes that occur in the CV system and their potential relationship to developing CV disease.…”

Toll-like receptor-4 signaling pathway in aorta aging and diseases: “its double nature”

“…This evidence is the result of findings from the Lakatta s' group, using rat models, [62,63], and Šabovic's group [64], who propose administering combination of low-dose fluvastatin and valsartan, as anti-aging drugs. On the other hand, the expression and activity of Ang II, the angiotensin converting enzyme (ACE), the Ang II receptor AT1 receptor within the aorta wall, in particular, in the thickened intima in several species, including humans, are risen as the age progress [62][63][64][65][66][67][68][69][70][71]. Interestingly, also the chymase, another angiotensin-convertase, was found in the wall of aged aorta [69].…”