Autophagy portends the level of cardiac hypertrophy in experimental hypertensive swine model

Xin Zhang, Matthew E. Gibson, Zi Lun Li, Xiang Yang Zhu, Kyra L. Jordan, Amir Lerman, Lilach O Lerman

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

BACKGROUND Left ventricular (LV) hypertrophy (LVH) plays an important role in hypertensive heart disease, and may be accompanied by myocardial autophagy. However, the pattern of autophagy during evolution of LVH is unclear. We hypothesized that autophagy activation indicates advancing cardiac LVH with tissue remodeling. METHODS Ten domestic pigs with a 10-week unilateral renovascular hypertension (HTN) were classified as mild or moderate HTN (n = 5 each group) based on the degree of renal artery stenosis (above or below 75%). Seven normal pigs served as controls. Left ventricular remodeling, function, and microvascular density were assessed using multi-detector- and micro-computed tomography and histology. Markers of myocardial autophagic and endoplasmic reticulum (ER) stress-related unfolded protein response (UPR), apoptosis, and fibrosis were examined ex vivo. RESULTS Both HTN groups had increased myocyte cross-sectional area, but it was greater in moderate HTN, accompanied by elevated LV muscle-mass. Moderate, but not mild HTN, also showed impaired microvascular density and impaired myocardial perfusion. Autophagy mediators were unaltered in mild HTN but UPR markers were increased, while in moderate HTN they were all upregulated, whereas UPR markers were suppressed. Myocardial apoptosis and fibrosis were also greater in moderate HTN. Autophagic proteins were correlated with LVH and fibrosis. CONCLUSIONS Autophagic activity is stimulated during the exacerbation of LVH, following a transient early increase in ER stress, and may be involved in the progression of cardiac remodeling in renovascular hypertensive heart disease.

Original languageEnglish (US)
Pages (from-to)81-89
Number of pages9
JournalAmerican Journal of Hypertension
Volume29
Issue number1
DOIs
StatePublished - Jan 1 2016

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Autophagy
Cardiomegaly
Swine
Hypertension
Unfolded Protein Response
Hypertrophy
Endoplasmic Reticulum Stress
Fibrosis
Heart Diseases
Apoptosis
Sus scrofa
Renovascular Hypertension
Renal Artery Obstruction
Ventricular Remodeling
Left Ventricular Hypertrophy
Left Ventricular Function
Muscle Cells
Histology
Perfusion
Tomography

Keywords

  • autophagy
  • blood pressure
  • hypertension
  • left ventricular hypertrophy
  • renal artery stenosis
  • renin-angiotensin-aldosterone system
  • unfolded protein response

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Autophagy portends the level of cardiac hypertrophy in experimental hypertensive swine model. / Zhang, Xin; Gibson, Matthew E.; Li, Zi Lun; Zhu, Xiang Yang; Jordan, Kyra L.; Lerman, Amir; Lerman, Lilach O.

In: American Journal of Hypertension, Vol. 29, No. 1, 01.01.2016, p. 81-89.

Research output: Contribution to journalArticle

Zhang, Xin ; Gibson, Matthew E. ; Li, Zi Lun ; Zhu, Xiang Yang ; Jordan, Kyra L. ; Lerman, Amir ; Lerman, Lilach O. / Autophagy portends the level of cardiac hypertrophy in experimental hypertensive swine model. In: American Journal of Hypertension. 2016 ; Vol. 29, No. 1. pp. 81-89.
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N2 - BACKGROUND Left ventricular (LV) hypertrophy (LVH) plays an important role in hypertensive heart disease, and may be accompanied by myocardial autophagy. However, the pattern of autophagy during evolution of LVH is unclear. We hypothesized that autophagy activation indicates advancing cardiac LVH with tissue remodeling. METHODS Ten domestic pigs with a 10-week unilateral renovascular hypertension (HTN) were classified as mild or moderate HTN (n = 5 each group) based on the degree of renal artery stenosis (above or below 75%). Seven normal pigs served as controls. Left ventricular remodeling, function, and microvascular density were assessed using multi-detector- and micro-computed tomography and histology. Markers of myocardial autophagic and endoplasmic reticulum (ER) stress-related unfolded protein response (UPR), apoptosis, and fibrosis were examined ex vivo. RESULTS Both HTN groups had increased myocyte cross-sectional area, but it was greater in moderate HTN, accompanied by elevated LV muscle-mass. Moderate, but not mild HTN, also showed impaired microvascular density and impaired myocardial perfusion. Autophagy mediators were unaltered in mild HTN but UPR markers were increased, while in moderate HTN they were all upregulated, whereas UPR markers were suppressed. Myocardial apoptosis and fibrosis were also greater in moderate HTN. Autophagic proteins were correlated with LVH and fibrosis. CONCLUSIONS Autophagic activity is stimulated during the exacerbation of LVH, following a transient early increase in ER stress, and may be involved in the progression of cardiac remodeling in renovascular hypertensive heart disease.

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