Secondary Coronary Artery Vasospasm Promotes Cardiomyopathy Progression

Matthew T. Wheeler, Claudia E. Korcarz, Keith A. Collins, Karen A. Lapidos, Andrew A. Hack, Matthew R. Lyons, Sara Zarnegar, Judy U. Earley, Roberto M. Lang, Elizabeth M. McNally*

*Corresponding author for this work

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Genetic defects in the plasma membrane-associated sarcoglycan complex produce cardiomyopathy characterized by focal degeneration. The infarct-like pattern of cardiac degeneration has led to the hypothesis that coronary artery vasospasm underlies cardiomyopathy in this disorder. We evaluated the coronary vasculature of γ-sarcoglycan mutant mice and found microvascular filling defects consistent with arterial vasospasm. However, the vascular smooth muscle sarcoglycan complex was intact in the coronary arteries of γ-sarcoglycan hearts with perturbation of the sarcoglycan complex only within the adjacent myocytes. Thus, in this model, coronary artery vasospasm derives from a vascular smooth muscle-cell extrinsic process. To reduce this secondary vasospasm, we treated γ-sarcoglycan-deficient mice with the calcium channel antagonist verapamil. Verapamil treatment eliminated evidence of vasospasm and ameliorated histological and functional evidence of cardiomyopathic progression. Echocardiography of verapamil-treated, γ-sarcoglycan-null mice showed an improvement in left ventricular fractional shortening (44.3 ± 13.3% treated versus 37.4 ± 15.3% untreated), maximal velocity at the aortic outflow tract (114.9 ± 27.9 cm/second versus 92.8 ± 22.7 cm/second), and cardiac index (1.06 ± 0.30 ml/minute/g versus 0.67 ± 0.16 ml/minute/g, P < 0.05). These data indicate that secondary vasospasm contributes to the development of cardiomyopathy and is an important therapeutic target to limit cardiomyopathy progression.

Original languageEnglish (US)
Pages (from-to)1063-1071
Number of pages9
JournalAmerican Journal of Pathology
Volume164
Issue number3
DOIs
StatePublished - Mar 2004

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Secondary Coronary Artery Vasospasm Promotes Cardiomyopathy Progression'. Together they form a unique fingerprint.

Cite this