Salvianolic acid A eases atherosclerosis in mice by eliminating senescent vascular cells

In ApoE-deficient mice fed a high-fat diet and in cultured vascular smooth muscle cells, researchers examined how salvianolic acid A influences atherosclerosis. The team tested the compound alongside targeted overexpression or knockdown of heat shock protein 90 alpha. In cell cultures, salvianolic acid A inhibited heat shock protein 90 alpha, triggering the degradation of protein kinase B and activating PERK signaling. This reaction elevated endoplasmic reticulum-mitochondrial contacts, increased mitochondrial calcium uptake, and induced apoptosis in senescent vascular smooth muscle cells. In mice, treatment reduced the burden of senescent cells, decreased plaque size, and improved the stability of the fibrous cap. Smooth muscle cell-specific knockdown of heat shock protein 90 alpha reproduced these protective effects, whereas overexpressing the protein blocked the therapeutic actions of salvianolic acid A.