Atrophic cardiomyocyte signaling in hypertensive heart disease

German Kamalov, Wenyuan Zhao, Tieqiang Zhao, Yao Sun, Robert A. Ahokas, Tony Marion, Fahed Al Darazi, Ivan Gerling, Syamal Bhattacharya, Karl Weber

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Cardinal pathological features of hypertensive heart disease (HHD) include not only hypertrophied cardiomyocytes and foci of scattered microscopic scarring, a footprint of prior necrosis, but also small myocytes ensnared by fibrillar collagen where disuse atrophy with protein degradation would be predicted. Whether atrophic signaling is concordant with the appearance of HHD and involves oxidative and endoplasmic reticulum (ER) stress remains unexplored. Herein, we examine these possibilities focusing on the left ventricle and cardiomyocytes harvested from hypertensive rats receiving 4 weeks aldosterone/salt treatment (ALDOST) alone or together with ZnSO4, a nonvasoactive antioxidant, with the potential to attenuate atrophy and optimize hypertrophy. Compared with untreated age-/sex-/strain-matched controls, ALDOST was accompanied by (1) left ventricle hypertrophy with preserved systolic function; (2) concordant cardiomyocyte atrophy (<1000 μm2) found at sites bordering on fibrosis where they were reexpressing β-myosin heavy chain; and (3) upregulation of ubiquitin ligases, muscle RING-finger protein-1 and atrogin-1, and elevated 8-isoprostane and unfolded protein ER response with messenger RNA upregulation of stress markers. ZnSO4 cotreatment reduced lipid peroxidation, fibrosis, and the number of atrophic myocytes, together with a further increase in cell area and width of atrophied and hypertrophied myocytes, and improved systolic function but did not attenuate elevated blood pressure. We conclude that atrophic signaling, concordant with hypertrophy, occurs in the presence of a reparative fibrosis and induction of oxidative and ER stress at sites of scarring where myocytes are atrophied. ZnSO4 cotreatment in HHD with ALDOST attenuates the number of atrophic myocytes, optimizes size of atrophied and hypertrophied myocytes, and improves systolic function.

Original languageEnglish (US)
Pages (from-to)497-506
Number of pages10
JournalJournal of Cardiovascular Pharmacology
Volume62
Issue number6
DOIs
StatePublished - Dec 1 2013

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Cardiac Myocytes
Muscle Cells
Heart Diseases
Aldosterone
Hypertrophy
8-epi-prostaglandin F2alpha
Endoplasmic Reticulum Stress
Fibrosis
Salts
Heart Ventricles
Atrophy
Cicatrix
Up-Regulation
Atrophic Muscular Disorders
Fibrillar Collagens
Protein Unfolding
Myosin Heavy Chains
Ligases
Ubiquitin
Endoplasmic Reticulum

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Atrophic cardiomyocyte signaling in hypertensive heart disease. / Kamalov, German; Zhao, Wenyuan; Zhao, Tieqiang; Sun, Yao; Ahokas, Robert A.; Marion, Tony; Al Darazi, Fahed; Gerling, Ivan; Bhattacharya, Syamal; Weber, Karl.

In: Journal of Cardiovascular Pharmacology, Vol. 62, No. 6, 01.12.2013, p. 497-506.

Research output: Contribution to journalArticle

Kamalov, German ; Zhao, Wenyuan ; Zhao, Tieqiang ; Sun, Yao ; Ahokas, Robert A. ; Marion, Tony ; Al Darazi, Fahed ; Gerling, Ivan ; Bhattacharya, Syamal ; Weber, Karl. / Atrophic cardiomyocyte signaling in hypertensive heart disease. In: Journal of Cardiovascular Pharmacology. 2013 ; Vol. 62, No. 6. pp. 497-506.
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AU - Al Darazi, Fahed

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