Apoptosis in Human Acute Myocardial Infarction: The Rationale for Clinical Trials of Apoptosis Inhibition in Acute Myocardial Infarction

Abstract

The objective of the present review was to examine apoptosis in patients with acute myocardial infarction (MI) and to address (i) the prevalence of apoptosis in acute MI, (ii) techniques to determine apoptosis, (iii) time period from the onset of acute MI to the detection of apoptosis, (iv) criticisms about apoptosis in acute MI. A systematic literature search identified over 20 publications comprising over 400 patients. The prevalence of apoptosis varied from over 90% in nuclear imaging studies using annexin binding to 0.25% in an autopsy study using monoclonal antibody to single-stranded DNA. Apoptosis was present in 50-60% of infarcted hearts within 24 hours of MI (detected by Bax and activated caspase-3), 26% of myocytes in patients who died within 11 days of MI (pooled mean from 5 studies using only TUNEL staining), and 12% of the myocytes of patients who died, on average, 20 days after onset of MI (pooled mean from eight studies using dual staining with caspase-3 plus TUNEL). Criticisms of the TUNEL assay appear unjustified as TUNEL is at least 85% specific using caspase-3 activation as a marker of apoptosis. Taken together, DNA fragmentation on agarose gel electrophoresis, TUNEL staining of nuclei, caspase-3 activation, bcl-2 and Bax expression, and annexin V binding overwhelming support apoptotic cell death as an important component of MI. The amount of cardiac apoptosis correlates with the presence of heart failure and fatal arrhythmias. Heart failure as a complication of MI carries a high mortality and indicates the amount of myocardium lost during the infarct. Taken together, these findings suggest the need for clinical trials in acute MI to confirm whether inhibition of apoptosis can reduce patient morbidity and mortality.

Apple pectin, a dietary fiber, ameliorates myocardial injury by inhibiting apoptosis in a rat model of ischemia/reperfusion

“…To support the results of TUNEL staining, the amount of cleaved caspase-3 was assessed by immunohistochemistry [ 26 , 27 ] ( Fig. 3 ).…”

Methanol Extract of Cassia mimosoides var. nomame Attenuates Myocardial Injury by Inhibition of Apoptosis in a Rat Model of Ischemia-Reperfusion

“…To support the results of the TUNEL staining, the amount of cleaved casapse-3 was assessed by immunohistochemistry ( Fig. 4 ) ( 19 , 20 ). In the apoptotic pathways, cleaved caspase-3 (the active form of the caspase) is derived from procaspase-3 by the removal of prodomain.…”

Maternal High-Salt Intake During Pregnancy Reprogrammed Renin–Angiotensin System-Mediated Cardiomyocyte Apoptosis in the Adult Offspring Heart

“…It is well known that HS or high sodium in the body would affect cardiovascular systems via RAS pathways. 39,40 Thus, we measured key components of the systemic RAS in the offspring exposed to prenatal HS. The data showed that plasma angiotensin II and ACE levels were reduced only in the newborn exposed to prenatal HS; however, this reduction was back to normal in the 1-month old or 5-month old.…”