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IGF-1 degradation by mouse mast cell protease 4 promotes cell death and adverse cardiac remodeling days after a myocardial infarction

Tejada, Thor (author)
Emory Univ, Sch Med, Dept Med Cardiol, Atlanta, GA 30322 USA.
Tan, Lin (author)
Emory Univ, Sch Med, Dept Med Cardiol, Atlanta, GA 30322 USA.
Torres, Rebecca A. (author)
Emory Univ, Sch Med, Dept Med Cardiol, Atlanta, GA 30322 USA.
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Calvert, John W. (author)
Emory Univ, Sch Med, Dept Surg, Carlyle Fraser Heart Ctr, Atlanta, GA 30322 USA.
Lambert, Jonathan P. (author)
Emory Univ, Sch Med, Dept Surg, Carlyle Fraser Heart Ctr, Atlanta, GA 30322 USA.
Zaidi, Madiha (author)
Emory Univ, Sch Med, Dept Med Cardiol, Atlanta, GA 30322 USA.
Husain, Murtaza (author)
Emory Univ, Sch Med, Dept Med Cardiol, Atlanta, GA 30322 USA.
Berce, Maria D. (author)
Emory Univ, Sch Med, Dept Med Cardiol, Atlanta, GA 30322 USA.
Naib, Hussain (author)
Emory Univ, Sch Med, Dept Med Cardiol, Atlanta, GA 30322 USA.
Pejler, Gunnar (author)
Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden.,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB),Uppsala University
Åbrink, Magnus (author)
Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Inst för biomedicin och veterinär folkhälsovetenskap,Department of Biomedical Science and Veterinary Public Health,Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Uppsala, Sweden.
Graham, Robert M. (author)
Victor Chang Cardiac Res Inst, Sydney, NSW 2010, Australia.
Lefer, David J. (author)
Emory Univ, Sch Med, Dept Surg, Carlyle Fraser Heart Ctr, Atlanta, GA 30322 USA.
Naqvi, Nawazish (author)
Emory Univ, Sch Med, Dept Med Cardiol, Atlanta, GA 30322 USA.
Husain, Ahsan (author)
Emory Univ, Sch Med, Dept Med Cardiol, Atlanta, GA 30322 USA.
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Emory Univ, Sch Med, Dept Med Cardiol, Atlanta, GA 30322 USA Emory Univ, Sch Med, Dept Surg, Carlyle Fraser Heart Ctr, Atlanta, GA 30322 USA. (creator_code:org_t)
 
2016-06-06
2016
English.
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:25, s. 6949-6954
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Heart disease is a leading cause of death in adults. Here, we show that a few days after coronary artery ligation and reperfusion, the ischemia-injured heart elaborates the cardioprotective polypeptide, insulin-like growth factor-1 (IGF-1), which activates IGF-1 receptor prosurvival signaling and improves cardiac left ventricular systolic function. However, this signaling is antagonized by the chymase, mouse mast cell protease 4 (MMCP-4), which degrades IGF-1. We found that deletion of the gene encoding MMCP-4 (Mcpt4), markedly reduced late, but not early, infarct size by suppressing IGF-1 degradation and, consequently, diminished cardiac dysfunction and adverse structural remodeling. Our findings represent the first demonstration to our knowledge of tissue IGF-1 regulation through proteolytic degradation and suggest that chymase inhibition may be a viable therapeutic approach to enhance late cardioprotection in post-ischemic heart disease.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Keyword

insulin-like growth factor-1
chymase
mouse mast cell protease 4
ischemia-reperfusion injury
cardioprotection

Publication and Content Type

ref (subject category)
art (subject category)

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