Angiotensin II Induced Hypertension Induces DNA Damage Associated Gene Expression in Visceral Adipose

Advanced age remains the most important risk factor for the development of cardiovascular disease. Aging is also the major risk factor for hypertension and is associated with chronic inflammation and senescent cell accumulation. Cellular senescence, a state of irreversible cell cycle arrest, is characterized by cell cycle arrest and the secretion of inflammatory mediators known as the senescence-associated secretory phenotype (SASP). Senescent cells have been demonstrated to accumulate in the adipose tissue of old mice. Although cellular senescence plays a role in age-related vascular dysfunction, it is unknown whether hypertension can induce cellular senescence independent of age. PURPOSE: This study aims to determine whether Angiotensin (Ang) II-induced hypertension results in cellular senescence and SASP-related gene expression in visceral adipose tissue (VAT) mice. METHODS: C57BL/6 mice of both sexes, aged 4-6 months, were divided into two groups: an Ang II-treated group, which received Ang II (500 ng/kg/min) via subcutaneous osmotic pumps for 14 days (a protocol shown to induce hypertension), and a sham-treated group, which received vehicle solution under the same conditions. Using qPCR, we assessed genes that are associated with senescence Cdkn2a(p16), Cdkn1a (p21), and Trp53 (p53) and SASP associated inflammatory genes Interleukin-6 (Il6), Tumor-necrosis factor-α (Tnfa), interferon-γ (Ifng), CCL2 (Ccl2), and CCL5 (Ccl5) in the VAT using the ΔΔct method. Group Differences were assessed by unpaired t-test. Data are normalized to control group and are mean ± SEM. RESULTS: While the Ang II-treated group exhibited a significant increase in p53 expression, a marker of DNA damage (p = 0.04), there was no difference in the relative gene expression of p16 and p21 between the Ang II-treated and control groups (p = 0.43, p=0.14). Similarly, no significant differences were found in the relative gene expression of Il6, Tnfa, Ifng, Ccl2, and Ccl5 (p = 0.09, p = 0.09, p = 0.12, p=0.14 and p = 0.47, respectively). CONCLUSION: Our data suggests that Ang II induced hypertension may result in greater DNA damage (p53) a precursor to senescence/SASP. However, hypertension alone may not be sufficient to induce overall senescence and SASP.