Aggarwal Amitesh, Singh Safal
Department of Medicine, University College of Medical Sciences, University of Delhi & GTB Hospital, Delhi, India; Department of Preventive Cardiology, University College of Medical Sciences, University of Delhi & GTB Hospital, Delhi, India.
Heart Asia. 2011 Jan 1;3(1):26-30. doi: 10.1136/ha.2010.003129. eCollection 2011.
Atherosclerosis has been a target of much clinical and molecular research. As a result of this extensive research, it is amply clear that atherogenesis is a multifactorial process involving an interplay of metabolic, immune and inflammatory mechanisms. Antiatherosclerotic strategies are today aiming for a multipronged approach targeting each arm of this multifactorial process. The newer agents under development can be divided into three broad categories: anti-inflammatory agents, modulators of intermediary metabolism and antiatherosclerosis vaccines. Potential targets for anti-inflammatory agents include inhibition of conversion of low-density lipoprotein (LDL) to oxidised LDL, blocking or downregulation of cell adhesion molecules, chemokine modulation and macrophage receptor blockade. Beyond inhibition of plaque formation, efforts are also ongoing to develop agents which stabilise the plaque by increasing its fibrous content and inhibiting its disruption. So far as research in the sphere of intermediary metabolism is concerned, the focus is now primarily on raising high-density lipoprotein and promoting reverse cholesterol transport; potential targets include cholesteryl ester transfer protein, liver X-receptor, lecithin cholesterol acyltransferase and high-density lipoprotein mimetics. Acyl-coenzymeA: cholesterol acyltransferase is another enzyme whose selective and differential inhibition is under active investigation. The concept of immunisation against a non-communicable disease such as atherosclerosis is still in its nascent stages. However, with increasing evidence to suggest the role of antigen-specific T-cell-mediated immunity in atherogenesis, this approach is potentially promising. Possible antigens under evaluation include oxidised LDL and its subparticles, heat-shock proteins and cholesteryl ester transfer protein. With cardiovascular disease being the single leading cause of death worldwide, the development of a safe and successful antiatherosclerosis strategy (possibly employing a combination of agents acting at various levels) will indeed be a major 21st-century achievement.
动脉粥样硬化一直是众多临床和分子研究的目标。经过广泛研究，现已充分明确动脉粥样硬化的形成是一个多因素过程，涉及代谢、免疫和炎症机制的相互作用。如今，抗动脉粥样硬化策略旨在采取多管齐下的方法，针对这一多因素过程的各个环节。正在研发的新型药物可大致分为三大类：抗炎药、中间代谢调节剂和抗动脉粥样硬化疫苗。抗炎药的潜在靶点包括抑制低密度脂蛋白（LDL）向氧化型LDL的转化、阻断或下调细胞黏附分子、调节趋化因子以及阻断巨噬细胞受体。除了抑制斑块形成，人们还在努力研发通过增加斑块纤维成分并抑制其破裂来稳定斑块的药物。就中间代谢领域的研究而言，目前主要关注提高高密度脂蛋白水平并促进胆固醇逆向转运；潜在靶点包括胆固醇酯转运蛋白、肝脏X受体、卵磷脂胆固醇酰基转移酶和高密度脂蛋白模拟物。酰基辅酶A：胆固醇酰基转移酶是另一种正在积极研究其选择性和差异性抑制作用的酶。针对动脉粥样硬化等非传染性疾病进行免疫接种的概念仍处于初期阶段。然而，越来越多的证据表明抗原特异性T细胞介导的免疫在动脉粥样硬化形成中发挥作用，这种方法具有潜在的前景。正在评估的可能抗原包括氧化型LDL及其亚颗粒、热休克蛋白和胆固醇酯转运蛋白。鉴于心血管疾病是全球单一的首要死因，开发一种安全且成功的抗动脉粥样硬化策略（可能采用作用于不同层面的药物组合）无疑将是21世纪的一项重大成就。
