Key result
Novel CarMA framework adapts Koch's postulates to establish metalloproteinase causality in LV remodeling.
This review proposes a framework based on Koch's postulates to move beyond observational data and establish causal relationships for matrix metalloproteinases in cardiovascular disease.
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CarMA framework structures causality testing for MMPs in LV remodeling; leaves open experimental validation before clinical adoption.
The first matrix metalloproteinase (MMP) was described in 1962; and since the 1990s, cardiovascular research has focused on understanding how MMPs regulate many aspects of cardiovascular pathology from atherosclerosis formation to myocardial infarction and stroke. Although much information has been gleaned by these past reports, to a large degree MMP cardiovascular biology remains observational, with few studies homing in on cause and effect relationships. Koch's postulates were first developed in the 19th century as a way to establish microorganism function and were modified in the 20th century to include methods to establish molecular causality. In this review, we outline the concept for establishing a similar approach to determine causality in terms of MMP functions. We use left ventricular remodeling postmyocardial infarction as an example, but this approach will have broad applicability across both the cardiovascular and the MMP fields.
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Iyer et al. (2014) conducted a review in Left ventricular remodeling post-myocardial infarction. Matrix metalloproteinases (MMPs) was evaluated. A novel framework based on Koch's postulates, termed cardiac metalloproteinase actions (CarMA), is proposed to establish causality between matrix metalloproteinases and left ventricular remodeling.
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