Serotonin Effects on Expression of the LDL Receptor Family Member LR11 and 7-Ketocholesterol–Induced Apoptosis in Human Vascular Smooth Muscle Cells

We previously confirmed the effect of sarpogrelate hydrochloride (sarpogrelate), 5-hydroxytryptamine (5-HT) 2A receptor antagonist on cardio-ankle vascular index (CAVI) as a marker of systemic arterial stiffness. After 6 months of treatment with sarpogrelate for 35 type 2 diabetic patients, decreased CAVI, indicating the ameliorated arterial stiffness, was observed. Therefore, via 5-HT2A receptor blockade, sarpogrelate might effect as a vasoactive agent, as well as an inhibitor of platelet aggregation. 5-HT is a known mitogen for vascular smooth muscle cells (VSMCs). In addition, the pathogenic change of VSMCs such as dedifferentiation and proliferation/apoptosis represents one of the atherosclerotic changes. On the other hand, LR11, a mosaic LDL receptor family member, may involve in the invasion of VSMCs into neointimal thickening. We therefore investigated an in vitro study to clarify whether 5-HT was concerned to LR11 expression and apoptosis of human VSMCs induced by 7-ketocholesterol (7KCHO), a major oxidation product of cholesterol involved in plaque destabilization. Resultantly, 5-HT accelerated the proliferation of VSMCs, and this effect was suppressed by simultaneous addition of sarpogrelate. Sarpogrelate also attenuated the 5-HT–induced LR11 mRNA expression in VSMCs. Additionally, 5-HT attenuated the 7KCHO-induced apoptosis of VSMCs through caspase-dependent pathway. These results suggest new knowledge on the modification of human VSMCs induced by 5-HT