Ventricular Remodeling After Infarction and the Extracellular Collagen Matrix

Left ventricular (LV) remodeling after myocardial infarction (MI) contributes significantly to LV dilation and dysfunction, and disability and death. Two paradigms, pertinent to antiremodeling therapy after MI (Figure 1), have evolved over the last 3 decades. Paradigm 1, LV remodeling is a major mechanism for disability and death,1,2 has received a great deal of attention. In contrast, paradigm 2, remodeling of the extracellular collagen matrix (ECCM) plays a major role in LV remodeling,3–7 whereby decrease, disruption, and/or defective composition of the ECCM promote LV dilation and rupture,4 –7 has received little attention. A host of clinical trials showed that angiotensin-converting enzyme (ACE) inhibitors (ACE-Is) with or without aldosterone antagonists, angiotensin II (AngII) type 1 (AT1) receptor blockers (ARBs), -adrenergic blockers or reperfusion improve outcome in survivors of MI.8 –10 Concurrent evidence has underscored the importance of preserving the ECCM during healing after MI.2–7 However, the antifibrotic action of ACE-Is, aldosterone antagonists and ARBs on ECCM in the infarct zone (IZ) and noninfarct zone (NIZ),6,7,9,11 and the reperfusion-induced damage to the ECCM in the IZ,5,7,12 remain unreconciled with the benefits.8 –10,13 Nevertheless, excessive ECCM, as in dilated ischemic cardiomyopathy after remote MI,14,15 can contribute to LV diastolic dysfunction and poor outcome,6 suggesting that antifibrotic drugs that target excess ECCM might be a logical therapeutic approach. This review focuses on the role of the ECCM in the evolution of LV remodeling after MI and the potential impact of therapies that target the ECCM.