Bynagari-Settipalli Yamini S, Chari Ramya, Kilpatrick Laurie, Kunapuli Satya P
Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Cardiovasc Hematol Disord Drug Targets. 2010 Dec 1;10(4):292-308. doi: 10.2174/187152910793743869.
Cardiovascular diseases (CVDs) such as atherosclerosis, hypertension and diabetes, are major global health problems and one of the leading causes of death. Thrombosis associated with multiple CVDs such as atherosclerosis and diabetes further increase morbidity by causing myocardial infarction or stroke. The members of Protein Kinase C (PKC) family are serine threonine kinases, abundantly expressed in cells that maintain cardiovascular health. Studies done using pharmacological tools that block wide range of PKCs or specific PKC isoforms and PKC gene knockout animals revealed that these enzymes regulate critical functional responses in cardiovascular cells. Interestingly, PKC isotype activity is context specific and PKC isotypes may have opposing functional roles depending on cell type and cellular environment (eg., cardiomyocytes, platelets). Furthermore, precise structural differences that occur amongst these isoforms have lead to development of compounds that inhibit or activate specific PKC isoforms. Thus, it is feasible to enhance the protective effects of a PKC isoform, while minimizing the damage caused by other members of PKC family. In this review, we summarize the role of each of these PKC isoforms in various cardiovascular diseases. In addition, we detail the specific PKC isoform modulators, their mechanism of action and ability to treat cardiovascular diseases, as evaluated in animal models or human subjects.
心血管疾病（如动脉粥样硬化、高血压和糖尿病）是全球主要的健康问题，也是主要的死亡原因之一。与多种心血管疾病（如动脉粥样硬化和糖尿病）相关的血栓形成，会导致心肌梗死或中风，进而进一步增加发病率。蛋白激酶C（PKC）家族成员是丝氨酸苏氨酸激酶，在维持心血管健康的细胞中大量表达。使用阻断多种PKC或特定PKC亚型的药理学工具以及PKC基因敲除动物进行的研究表明，这些酶调节心血管细胞中的关键功能反应。有趣的是，PKC亚型的活性具有上下文特异性，并且根据细胞类型和细胞环境（例如心肌细胞、血小板），PKC亚型可能具有相反的功能作用。此外，这些亚型之间出现的精确结构差异导致了抑制或激活特定PKC亚型的化合物的开发。因此，增强PKC亚型的保护作用，同时将PKC家族其他成员造成的损害降至最低是可行的。在这篇综述中，我们总结了这些PKC亚型在各种心血管疾病中的作用。此外，我们详细介绍了特定的PKC亚型调节剂、它们的作用机制以及在动物模型或人类受试者中评估的治疗心血管疾病的能力。
