Cholesterol induced heart valve inflammation and injury: efficacy of cholesterol lowering treatment

BACKGROUND: Heart valves often undergo a degenerative process leading to mechanical dysfunction that requires valve replacement. This process has been compared with atherosclerosis because of shared pathology and risk factors. In this study, we aimed to elucidate the role of inflammation triggered by cholesterol infiltration and cholesterol crystals formation causing mechanical and biochemical injury in heart valves. METHODS: Human and atherosclerotic rabbit heart valves were evaluated. New Zealand White male rabbits were fed an enriched cholesterol diet alone or with simvastatin and ezetimibe simultaneous or after 6 months of initiating cholesterol diet. Inflammation was measured using C-reactive protein (CRP) and RAM 11 of tissue macrophage content. Cholesterol crystal presence and content in valves was evaluated using scanning electron microscopy. RESULTS: Cholesterol diet alone induced cholesterol infiltration of valves with associated increased inflammation. Tissue cholesterol, CRP levels and RAM 11 were significantly lower in simvastatin and ezetimibe rabbit groups compared with cholesterol diet alone. However, the treatment was effective only when initiated with a cholesterol diet but not after lipid infiltration in valves. Aortic valve cholesterol content was significantly greater than all other cardiac valves. Extensive amounts of cholesterol crystals were noted in rabbit valves on cholesterol diet and in diseased human valves. CONCLUSIONS: Prevention of valve infiltration with cholesterol and reduced inflammation by simvastatin and ezetimibe was effective only when given during the initiation of high cholesterol diet but was not effective when given following infiltration of cholesterol into the valve matrix

Role of Cholesterol Crystals During Acute Myocardial Infarction and Cerebrovascular Accident

Cholesterol crystals have long been recognized as part of atherosclerotic plaques. They have been visualized by light microscopy as empty spaces or imprints where crystals were once present and then dissolved by tissue processing. Thus, until now, their role in atherosclerosis and plaque rupture had been considered to be inert. However, by the processing of tissue without ethanol it was possible to visualize their extensiveness and potential role in tissue injury. Also, it was demonstrated that cholesterol expands in volume when crystallizing from the liquid to the solid state, which is the presumed cause of plaque rupture by sharp-tipped crystals growing out of the plaque’s necrotic core. Specifically, in patients who died of myocardial infarction, all culprit coronary lesions had extensive cholesterol crystals perforating the fibrous cap and intima, while those patients who died of other causes and had plaques did not have crystals perforating the cap and intima. Additionally, cholesterol crystals traveling downstream from the plaque rupture site can scrape the endothelium and promote vasospasm. Moreover, cholesterol crystals lodging into the muscle can trigger an inflammation with necrosis independent of circulatory compromise or ischemia. These findings suggest that cholesterol crystals could play a critical role in plaque rupture, as well as vascular and myocardial injury