Left ventricular remodeling in the post-infarction heart: a review of cellular, molecular mechanisms, and therapeutic modalities.
As more patients survive myocardial infarctions, the incidence of heart failure increases. After an infarction, the human heart undergoes a series of structural changes, which are governed by cellular and molecular mechanisms in a pathological metamorphosis termed "remodeling." This review will discuss the current developments in our understanding of these molecular and cellular events in remodeling and the various pharmacological, cellular and device therapies used to treat, and potentially retard, this condition. Specifically, this paper will examine the neurohormonal activity of the renin-angiotensin-aldosterone axis and its molecular effects on the heart. The emerging understanding of the extra-cellular matrix and the various active molecules within it, such as the matrix metalloproteinases, elicits new appreciation for their role in cardiac remodeling and as possible future therapeutic targets. Cell therapy with stem cells is another recent therapy with great potential in improving post-infarcted hearts. Lastly, the cellular and molecular effects of left ventricular assist devices on remodeling will be reviewed. Our increasing knowledge of the cellular and molecular mechanisms underlying cardiac remodeling enables us not only to better understand how our more successful therapies, like angiotensin-converting enzyme inhibitors, work, but also to explore new therapies of the future.
Gajarsa
Jason J
JJ
Division of Cardiology, Department of Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA.
Kloner
Robert A
RA
D000293:Adolescent; D000328:Adult; D000368:Aged; D064987:Cell- and Tissue-Based Therapy; D005109:Extracellular Matrix; D005260:Female; D006333:Heart Failure / Q000473:pathology / Q000628:therapy*; D006352:Heart Ventricles / Q000166:cytology / Q000473:pathology*; D006353:Heart-Assist Devices; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications* / Q000473:pathology / Q000628:therapy; D009206:Myocardium / Q000166:cytology / Q000473:pathology; D018377:Neurotransmitter Agents; D012084:Renin-Angiotensin System / Q000187:drug effects; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000209:etiology*; D020257:Ventricular Remodeling; D055815:Young Adult
D018377:Neurotransmitter Agents