Novel mechanisms for caspase inhibition protecting cardiac function with chronic pressure overload

Misun Park, Stephen F. Vatner, Lin Yan, Shumin Gao, Seunghun Yoon, Grace Jung Ah Lee, Lai Hua Xie, Richard N. Kitsis, Dorothy E. Vatner

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Myocyte apoptosis is considered a major mechanism in the pathogenesis of heart failure. Accordingly, manipulations that inhibit apoptosis are assumed to preserve cardiac function by maintaining myocyte numbers. We tested this assumption by examining the effects of caspase inhibition (CI) on cardiac structure and function in C57BL/6 mouse with pressure overload model induced by transverse aortic constriction (TAC). CI preserved left ventricular (LV) function following TAC compared with the vehicle. TAC increased apoptosis in non-myocytes more than in myocytes and these increases were blunted more in non-myocytes by CI. Total myocyte number, however, did not differ significantly among control and TAC groups and there was no correlation between myocyte number and apoptosis, but there was a strong correlation between myocyte number and an index of myocyte proliferation, Ki67-positive myocytes. Despite comparable pressure gradients, LV hypertrophy was less in the CI group, likely attributable to decreased wall stress. Since changes in myocyte numbers did not account for protection from TAC, several other CI-mediated mechanisms were identified including: (a) lessening of TAC-induced fibrosis, (b) augmentation of isolated myocyte contractility, and (c) increased angiogenesis and Ki67-positive myocytes, which were due almost entirely to the non-myocyte apoptosis, but not myocyte apoptosis, with CI. CI maintained LV function following TAC not by protecting against myocyte loss, but rather by augmenting myocyte contractile function, myocyte proliferation, and angiogenesis resulting in reduced LV wall stress, hypertrophy, and fibrosis.

Original languageEnglish (US)
Article number324
JournalBasic Research in Cardiology
Volume108
Issue number1
DOIs
StatePublished - 2013

Fingerprint

Caspases
Muscle Cells
Pressure
Constriction
Apoptosis
Left Ventricular Function
Fibrosis
Left Ventricular Hypertrophy
Inbred C57BL Mouse
Hypertrophy
Heart Failure

Keywords

  • Angiogenesis
  • Apoptosis inhibition
  • Cardiac hypertrophy
  • Fibrosis
  • Myogenesis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

Cite this

Park, M., Vatner, S. F., Yan, L., Gao, S., Yoon, S., Lee, G. J. A., ... Vatner, D. E. (2013). Novel mechanisms for caspase inhibition protecting cardiac function with chronic pressure overload. Basic Research in Cardiology, 108(1), [324]. https://doi.org/10.1007/s00395-012-0324-y

Novel mechanisms for caspase inhibition protecting cardiac function with chronic pressure overload. / Park, Misun; Vatner, Stephen F.; Yan, Lin; Gao, Shumin; Yoon, Seunghun; Lee, Grace Jung Ah; Xie, Lai Hua; Kitsis, Richard N.; Vatner, Dorothy E.

In: Basic Research in Cardiology, Vol. 108, No. 1, 324, 2013.

Research output: Contribution to journalArticle

Park, Misun ; Vatner, Stephen F. ; Yan, Lin ; Gao, Shumin ; Yoon, Seunghun ; Lee, Grace Jung Ah ; Xie, Lai Hua ; Kitsis, Richard N. ; Vatner, Dorothy E. / Novel mechanisms for caspase inhibition protecting cardiac function with chronic pressure overload. In: Basic Research in Cardiology. 2013 ; Vol. 108, No. 1.
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