Journal
AMERICAN JOURNAL OF THE MEDICAL SCIENCES
Volume 348, Issue 4, Pages 337-346Publisher
ELSEVIER SCIENCE INC
DOI: 10.1097/MAJ.0000000000000255
Keywords
Mitral regurgitation; Volume overload; Extracellular matrix; inflammation; Adrenergic drive; Oxidative stress; LV dysfunction; LV remodeling
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Funding
- NHLBI NIH HHS [R01 HL097176, P50 HL077100] Funding Source: Medline
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Mitral regurgitation and other conditions marked by a pure isolated volume overload (VO) of the heart result in a progressive form of eccentric left ventricular remodeling and dysfunction. As opposed to the more extensively studied pressure overload, there are no approved medical therapies because an understanding of the underlying pathological mechanisms at work in VO is lacking. Over the past 20 years, our laboratory has identified multiple key biological functions involved in the pathological remodeling in VO. Specifically, we have noted perturbed matrix homeostasis, detrimental adrenergic signaling, increased intracellular reactive oxygen species and an intense inflammatory response that implicates mast cells and their product chymase, which seems to cause extensive remodeling both inside and outside the cardiomyocyte. How these multiple pathways intersect over the course of VO and their response to various single and combined interventions are now the subject of intense investigation.
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