The role of angiotensin II in cardiovascular disease-induced cancer growth

BACKGROUND: The higher incidence of cancer in patients with cardiovascular disease (CVD) has historically been explained by shared risk factors. Recent studies suggest, however, a causal relationship. Nevertheless, the mechanisms of CVD-induced cancer are incompletely understood. Here, we hypothesize that angiotensin II (ANGII) links CVD and increased cancer growth. OBJECTIVE: We investigated the impact of ANGII-induced CVD on cancer growth in vivo, differentiating between a direct effect of ANGII on tumor cells or indirect effects secondary to CVD. METHODS: mice and (iii) comparing the impact of ANGII on tumor growth in high (LLC) and low (MC38) angiotensin II receptor type I (AT1) expressing tumor cells. RESULTS: mice, even at a low dose that did not induce LV hypertrophy or cardiac fibrosis. Lastly, an analysis of publicly available cancer databases showed that AT1 gene copy number variation is increased in most human cancer lines and tumors. CONCLUSION: This study indicates that ANGII has direct effects on cancer growth, warranting further research into the role of an activated renin-angiotensin-aldosterone-system (RAAS) as a mechanistic link between CVD and cancer growth in AT1-positive tumors.