Renin-Angiotensin System Role in Cardiovascular Effects of Plasticizers: A Systematic Review

Plasticizers, particularly bisphenols and phthalates, are prevalent additives in plastic products that enhance durability, shape, and flexibility. However, bisphenols and phthalates have been associated with adverse health effects. Recent studies linked these plasticizers to cardiovascular diseases, implicating the Renin-Angiotensin System (RAS) as a potential mediator of these effects. This review explores the relationship between plasticizer exposure and RAS modulation, focusing on cardiovascular outcomes. A systematic search was conducted in PubMed up to November 2024 according to the PRISMA guideline. The words used in this research were bisphenol, phthalates, angiotensin-converting enzyme, angiotensin II type 1 receptor, angiotensin, angiotensinogen, renin-angiotensin system, heart, cardio* (cardiovascular terms), hypertension, and blood pressure to find all relevant articles published. Thirty-one studies were screened based on inclusion and exclusion criteria, and thirteen articles were included in this systematic review. In different experimental models, several cardiovascular effects were associated with exposure to different doses of Bisphenol A (BPA) and phthalates due to the overactivation of the classical axis of the RAS. BPA exposure led to hypertension, vascular cell proliferation, and oxidative stress, and aggravated hypertensive and malnourishment conditions. In animal models, phthalates increased blood pressure, vascular thickening, and cardiac hypertrophy. These effects were partially reduced by ACE inhibition, highlighting the critical role of the RAS in plasticizer-induced cardiovascular outcomes (hypertension, smooth muscle cell proliferation, cardiac hypertrophy and fibrosis, and cardiovascular inflammation). The role of the counterregulatory axis of the RAS and the effects of emerging plasticizer analogs on cardiovascular health should be addressed by future investigations.