Gluba-Brzózka Anna, Franczyk Beata, Rysz-Górzyńska Magdalena, Ławiński Janusz, Rysz Jacek
Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland.
Department of Ophthalmology and Visual Rehabilitation, Medical University of Lodz, 90-549 Lodz, Poland.
Int J Mol Sci. 2021 Nov 9;22(22):12109. doi: 10.3390/ijms222212109.
Cardiovascular disease (CAD) is the main cause of morbidity and deaths in the western world. The development of atherosclerosis underlying CAD development begins early in human life. There are numerous genetic and environmental risk factors accelerating its progression which then leads to the occurrence of acute events. Despite considerable progress in determining risk factors, there is still a lot of work ahead since identified determinants are responsible only for a part of overall CAD risk. Current therapies are insufficient to successfully reduce the risk of atherosclerosis development. Therefore, there is a need for effective preventive measures of clinical manifestations of atherosclerosis since the currently available drugs cannot prevent the occurrence of even 70% of clinical events. The shift of the target from lipid metabolism has opened the door to many new therapeutic targets. Currently, the majority of known targets for anti-atherosclerotic drugs focus also on inflammation (a common mediator of many risk factors), mechanisms of innate and adaptive immunity in atherosclerosis, molecule scavengers, etc. The therapeutic potential of cyclodextrins, protein kinase inhibitors, colchicine, inhibitors of p38 mitogen-activated protein kinase (MAPK), lipid dicarbonyl scavengers, a monoclonal antibody targeting interleukin-1β, and P-selectin inhibitors is still not fully confirmed and requires confirmation in large clinical trials. The preliminary results look promising.
心血管疾病(CAD)是西方世界发病和死亡的主要原因。CAD发展所基于的动脉粥样硬化在人类生命早期就开始发展。有许多遗传和环境风险因素会加速其进程,进而导致急性事件的发生。尽管在确定风险因素方面取得了相当大的进展,但仍有许多工作要做,因为已确定的决定因素仅占CAD总体风险的一部分。目前的治疗方法不足以成功降低动脉粥样硬化发展的风险。因此,需要采取有效的动脉粥样硬化临床表现预防措施,因为目前可用的药物甚至无法预防70%的临床事件的发生。治疗靶点从脂质代谢的转变为许多新的治疗靶点打开了大门。目前,大多数已知的抗动脉粥样硬化药物靶点也集中在炎症(许多风险因素的常见介质)、动脉粥样硬化中的固有免疫和适应性免疫机制、分子清除剂等方面。环糊精、蛋白激酶抑制剂、秋水仙碱、p38丝裂原活化蛋白激酶(MAPK)抑制剂、脂质二羰基清除剂、靶向白细胞介素-1β的单克隆抗体和P-选择素抑制剂的治疗潜力仍未得到充分证实,需要在大型临床试验中得到证实。初步结果看起来很有希望。