1 Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Experimentale et Clinique (IREC), Université catholique de Louvain , Brussels, Belgium .
Antioxid Redox Signal. 2014 Mar 10;20(8):1216-37. doi: 10.1089/ars.2013.5537. Epub 2013 Sep 28.
Cardiovascular diseases (CVD) represent a major public health burden. High low-density lipoprotein (LDL)-cholesterol is a recognized pathogenic factor for atherosclerosis, and its complications and statins represent the most potent and widely used therapeutic approach to prevent and control these disorders.
A number of clinical and experimental studies concur to identify endothelial dysfunction as a primary step in the development of atherosclerosis, as well as a risk factor for subsequent clinical events. Oxidant stress resulting from chronic elevation of plasma LDL-cholesterol (LDL-chol) is a major contributor to both endothelial dysfunction and its complications, for example, through alterations of endothelial nitric oxide signaling.
Statin treatment reduces morbidity and mortality of CVD, but increasing evidence questions that this is exclusively through reduction of plasma LDL-chol. The identification of ancillary effects on (cardio)vascular biology, for example, through their modulation of oxidative stress, will not only increase our understanding of their mechanisms of action, with a potential broadening of their indication(s), but also lead to the identification of new molecular targets for future therapeutic developments in CVD.
Further characterization of molecular pathways targeted by statins, for example, not directly mediated by changes in plasma lipid concentrations, should enable a more comprehensive approach to the pathogenesis of (cardio)vascular disease, including, for example, epigenetic regulation and fine tuning of cell metabolism.
心血管疾病（CVD）是一个主要的公共卫生负担。低高密度脂蛋白（LDL）-胆固醇是动脉粥样硬化的一个公认的致病因素，其并发症和他汀类药物是预防和控制这些疾病最有效和最广泛使用的治疗方法。
许多临床和实验研究都认为内皮功能障碍是动脉粥样硬化发展的第一步，也是随后发生临床事件的一个危险因素。由于血浆 LDL-胆固醇（LDL-chol）的慢性升高导致的氧化应激是内皮功能障碍及其并发症的一个主要原因，例如通过改变内皮一氧化氮信号。
他汀类药物治疗降低了 CVD 的发病率和死亡率，但越来越多的证据表明，这不仅仅是通过降低血浆 LDL-chol 来实现的。对（心血管）生物学的辅助作用的鉴定，例如通过其对氧化应激的调节，不仅将增加我们对其作用机制的理解，有可能扩大其适应证，而且还将导致为 CVD 的未来治疗发展确定新的分子靶标。
进一步描述他汀类药物作用的分子途径，例如，不是直接通过改变血浆脂质浓度介导的，应该能够更全面地了解（心血管）疾病的发病机制，包括例如表观遗传调控和细胞代谢的微调。
