Myocyte Cell Death in the Diseased Heart

From the Department of Medicine, New York Medical College, Valhalla.

Key Words: necrosis • apoptosis • myocyte

In this issue of Circulation Research, Karwatowska-Prokopczuk et al¹ and Takemura et al² report, respectively, that inhibition of the vacuolar proton ATPase (VPATPase) enhances apoptosis in neonatal cardiac myocytes during metabolic recovery and that the progression of the healing process after infarction involves apoptotic death of inflammatory and interstitial cells. We will discuss these 2 studies separately, because the first addresses important mechanisms of myocyte death and survival, and the second provides new information on scarring of the postinfarcted heart. Both studies emphasize directly or indirectly through in vitro¹ and in vivo² experiments the role of apoptosis in ischemic injury. Two different phases of cardiac damage are examined: myocyte death and reparative fibrosis. In the first article,¹ the recognition that alkalinization of myocytes is regulated not only by activation of the Na⁺-H⁺ antiport and the Na⁺-HCO₃^- symport but also via a third proton-extruding system, VPATPase,^1,3 may elucidate some of the critical events affecting the ischemic myocardium. Whether myocardial ischemia occurs in vivo in the absence^4,5 or presence^5,6 of reperfusion, cell death by apoptosis is the predominant pathological consequence; its etiology, however, remains to be defined. Similarly, the paradoxical beneficial impact of Na⁺-H⁺ exchange inhibition during ischemia¹ is unclear. The documentation that the ATP-dependent vacuolar proton pump may play a role in hypoxia-induced myocyte apoptosis is significant because it points to alterations in pH_i as critical for the transmission of a death signal to myocytes in vivo. Impairment of VPATPase affects the extrusion of protons from the . . . [Full Text of this Article]

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