Using the laws of thermodynamics to understand how matrix metalloproteinases coordinate the myocardial response to injury

Abstract:

Following myocardial infarction (MI), the left ventricle (LV) undergoes a series of molecular, cellular, and functional alterations that are both part of the wound healing response to form a scar in the infarct region and the consequence of that response. Using the laws of thermodynamics as an analogy, we present here three laws for categorizing the post-MI LV remodeling process. The first law is that the LV will attempt to maintain equilibrium and compensate as a way to maximize function, the second law is that remodeling is progressive and unidirectional, and the third law is that the final goal is (ideally, but not always achievable) a stable, equilibrated scar. This comparison helps to define the boundaries of the system, whether it be the infarct zone, the LV, the heart, or the entire body. This review provides an overview for those not directly in the field and establishes a framework to help prioritize future research directions.

Keywords::

• MMP
• remodeling
• left ventricle
• inflammation
• fibrosis
• extracellular matrix
• proteomics

Acknowledgments

This work was supported by American Heart Association Postdoctoral Grant 14POST18770012 to RPI; the National Institutes of Health HHSN 268201000036C (N01-HV-00244), HL075360, and GM114833 to MLL, P01HL051971, and P20GM104357; and the Biomedical Laboratory Research and Development Service of the Veterans Affairs Office of Research and Development Award 5I01BX000505 to MLL.

Disclosure

The authors report no conflicts of interest in this work.