Pathways of matrix metalloproteinase induction in heart failure: bioactive molecules and transcriptional regulation.

ABSTRACT

The structural basis for the development of congestive heart failure (CHF) is a maladaptive myocardial remodeling process which occurs secondarily to post-myocardial infarction (MI), hypertensive hypertrophy, or cardiomyopathy. Both cellular and extracellular factors are involved in the remodeling process and it is the combined action of these factors giving rise to changes in myocardial structure which eventually affects function. One component in this remodeling process is a family of extracellular matrix degrading enzymes, the matrix metalloproteinases or MMPs. Many bioactive molecules such as cytokines/chemokines, bioactive peptides, and neurohormones which are operative in CHF likely contribute to the induction of MMPs. For example, a specific cassette of transcription factors is likely induced with extracellular stimuli in the context of CHF which in turn induces MMPs and contributes to the maladaptive remodeling process. This review will briefly discuss the biology of the MMP family, but will more importantly identify how biological factors active in CHF result in the modulation of the MMP family. Understanding how upstream molecules are involved in MMP regulation/dysregulation may provide an avenue to develop important therapeutic interventions.