本期播客深入探讨了高密度脂蛋白(HDL)的生物学特性及其与动脉粥样硬化性心血管疾病(ASCVD)的关系。宾夕法尼亚大学医学院教授Dan Rader详细介绍了HDL的起源、代谢、功能，以及高HDL-C水平并不直接等同于低心血管疾病风险的原因。他还揭示了衡量HDL功能以预测疾病风险的更好方法，并探讨了HDL在逆向胆固醇转运中的作用及其对降低ASCVD的益处。此外，Dan还讨论了HDL胆固醇与神经退行性疾病之间的最新关联，并展望了HDL研究对未来治疗干预的积极前景。

🧬 HDL的起源与结构：HDL是一种脂蛋白，其在体内的生成和结构对于其功能至关重要。文章介绍了HDL的生成过程，以及其在脂蛋白代谢中的关键作用。

🔄 HDL代谢与功能：HDL的代谢过程，包括胆固醇的逆向转运，对于维持血管健康至关重要。文章详细解释了HDL如何从细胞中清除胆固醇，并将其转运至肝脏进行代谢。

💔 HDL与心血管疾病风险：虽然高HDL-C水平曾被认为是降低心血管疾病风险的指标，但研究表明，HDL的功能比其水平更能预测疾病风险。文章探讨了HDL功能性评估的重要性，并介绍了SR-B1等相关受体。

🧠 HDL与神经退行性疾病：文章还提到了HDL与神经退行性疾病之间的关联，这为HDL研究开辟了新的方向，并探讨了HDL在神经系统健康中的潜在作用。

🧪 未来研究与治疗：文章最后展望了HDL研究的未来，并讨论了有前景的干预措施，这些措施可能促进胆固醇外流和逆向转运，为心血管疾病和神经退行性疾病的治疗提供了新的希望。

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Dan Rader is a Professor at the Perelman School of Medicine at the University of Pennsylvania, where he conducts translational research on lipoprotein metabolism and atherosclerosis with a particular focus on the function of high-density lipoproteins (HDLs). In this episode, Dan goes in-depth on HDL biology, including the genesis of HDL, its metabolism, function, and how this relates to atherosclerotic cardiovascular disease (ASCVD). He explains why having high HDL-C levels does not directly translate to a low risk of cardiovascular disease and reveals research pointing to a better way to measure the functionality of HDL and predict disease risk. He also goes into detail on the role of HDL in reverse cholesterol transport and the benefits this has for reducing ASCVD. Additionally, Dan discusses the latest thinking around the association between HDL cholesterol and neurodegenerative diseases and ends the conversation with a discussion of how the latest research on HDL provides a promising outlook for ongoing trials and future therapeutic interventions.

We discuss:

The lipidology of apoB and apoA [4:00]; A primer on the high-density lipoprotein (HDL): genesis, structure, and more [9:30]; How the lipoprotein system differs in humans compared to other mammals [20:00]; Clarifying the terminology around HDL and apoA [25:30]; HDL metabolism [31:45]; CETP inhibitors for raising HDL-C: does it reduce CVD risk? [34:45]; Why it’s so important to have hard outcome trials in the field of cardiovascular medicine [42:30]; SR-B1: an HDL receptor important for cholesterol efflux [48:00]; The association between HDL levels and atherosclerosis: are they causally linked? [53:15]; How insulin resistance is impacting HDL, and how HDL-C provides insights into triglyceride metabolism [58:00]; Disappointing results from the studies of niacin—a drug that raises HDL-C and lowers apoB [1:08:15]; HDL lipidation, dilapidation, and reverse cholesterol transport [1:12:00]; Measuring the cholesterol efflux capacity of HDL: a better predictor of ASCVD risk than HDL-C? [1:22:00]; A promising new intervention that may promote cholesterol efflux and reverse cholesterol transport [1:32:45]; The association between HDL cholesterol and neurodegenerative diseases [1:34:00]; Challenges ahead, a promising outlook, and the next frontier in lipidology [1:44:45]; and More.

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