Don't lose heart ‐ therapeutic value of apoptosis prevention in the treatment of cardiovascular disease

• Published in: Journal of cellular and molecular medicine 2005-07, Vol.9 (3), p.609-622
• Main Authors: Reeve, Janice L. V., Duffy, Angela M., O'Brien, Timothy, Samali, Afshin
• Format: Article
• Language: English
• Subjects: Animals; anti‐apoptosis; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Apoptosis Review Series; Calcium signalling; Cardiomyocytes; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - pathology; Cardiovascular Diseases - therapy; CASP8 and FADD-Like Apoptosis Regulating Protein; Caspase Inhibitors; Cell death; Congestive heart failure; Death receptors; Drug therapy; Endoplasmic reticulum; Growth factors; Health aspects; Heart attack; Heart diseases; Heat shock proteins; Heat-Shock Proteins - physiology; Humans; Intracellular Signaling Peptides and Proteins - physiology; ischemia/reperfusion (I/R); mitochondria; Models, Biological; Myocardial infarction; Myocardium; Myocytes; Oxidants; Prevention; Proteins; Proto-Oncogene Proteins c-bcl-2 - physiology; Receptor mechanisms; Signal transduction; Stress proteins; therapy; Trimetazidine
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/j.1582-4934.2005.tb00492.x

Cardiovascular disease is a leading cause of death worldwide. Loss of function or death of cardiomyocytes is a major contributing factor to these diseases. Cell death in conditions such as heart failure and myocardial infarction is associated with apoptosis. Apoptotic pathways have been well studied in non‐myocytes and it is thought that similar pathways exist in cardiomyocytes. These pathways include death initiated by ligation of membrane‐bound death receptors, release of pro‐apoptotic factors from mitochondria or stress at the endoplasmic reticulum. The key regulators of apoptosis include inhibitors of caspases (IAPs), the Bc1‐2 family of proteins, growth factors, stress proteins, calcium and oxidants. The highly organized and predictive nature of apoptotic signaling means it is amenable to manipulation. A thorough understanding of the apoptotic process would facilitate intervention at the most suitable points, alleviating myocardium decline and dysfunction. This review summarizes the mechanisms underlying apoptosis and the mediators/regulators involved in these signaling pathways. We also discuss how the potential therapeutic value of these molecules could be harnessed.