Mechanical stress-induced apoptosis in the cardiovascular system.
All tissues in the body are subjected to physical forces originating either from tension, created by cells themselves, or from the environment. Particularly, the cardiovascular system is continuously subjected to haemodynamic forces created by blood flow and blood pressure. While biomechanical force at physiological levels is essential to develop and maintain organic structure and function, elevated mechanical stress may result in cell death leading to pathological conditions. In recent years, however, it has been widely recognized that cell death, namely apoptosis, is not just the response to an injury but a highly regulated and controlled process. Therefore, physical stimuli must be sensed by cells and transmitted through intracellular signal transduction pathways to the nucleus, resulting in cell apoptosis. Disturbances in the regulatory mechanisms of apoptosis often precede the development of a disease. Exploration of the molecular signalling mechanisms leading to mechanical stress-induced apoptosis in cardiovascular disorders revealed the crucial role of apoptosis in the pathogenesis of these diseases. For instance, heart failure, hypertension and atherosclerosis are believed to be related to sustained mechanical overloading or stress. In this review we summarize the recent data focusing on molecular mechanisms of mechanical stress-induced apoptosis and highlight the role of apoptosis in the development of cardiovascular disorders, which may lead to new therapeutic strategies for these diseases.
Wernig
Florian
F
Department of Cardiological Sciences, St George's Hospital Medical School, Cranmer Terrace, Tooting, London SW17 0RE, UK.
Xu
Qingbo
Q
D000818:Animals; D017209:Apoptosis; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000473:pathology; D002319:Cardiovascular System / Q000378:metabolism* / Q000473:pathology*; D002470:Cell Survival; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction; D013314:Stress, Mechanical; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53