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Macrophages dictate the progression and manifestation of hypertensive heart disease.
Kain, David; Amit, Uri; Yagil, Chana; Landa, Natalie; Naftali-Shani, Nili; Molotski, Natali; Aviv, Vered; Feinberg, Micha S; Goitein, Orly; Kushnir, Tammar; Konen, Eli; Epstein, Fredrik H; Yagil, Yoram; Leor, Jonathan.
Afiliação
  • Kain D; Tamman Cardiovascular Research Institute, Sheba Medical Center, Tel-Hashomer, Israel; Neufeld Cardiac Research Institute, Tel-Aviv University, Sheba Medical Center, Tel-Hashomer, Israel; Sheba Center for Regenerative Medicine, Stem Cell, and Tissue Engineering, Tel Hashomer, Israel.
  • Amit U; Tamman Cardiovascular Research Institute, Sheba Medical Center, Tel-Hashomer, Israel; Neufeld Cardiac Research Institute, Tel-Aviv University, Sheba Medical Center, Tel-Hashomer, Israel; Sheba Center for Regenerative Medicine, Stem Cell, and Tissue Engineering, Tel Hashomer, Israel.
  • Yagil C; Laboratory for Molecular Medicine and Israeli Rat Genome Center, Faculty of Health Sciences, Ben-Gurion University, Barzilai Medical Center Campus, Ashkelon, Israel.
  • Landa N; Tamman Cardiovascular Research Institute, Sheba Medical Center, Tel-Hashomer, Israel; Neufeld Cardiac Research Institute, Tel-Aviv University, Sheba Medical Center, Tel-Hashomer, Israel; Sheba Center for Regenerative Medicine, Stem Cell, and Tissue Engineering, Tel Hashomer, Israel.
  • Naftali-Shani N; Tamman Cardiovascular Research Institute, Sheba Medical Center, Tel-Hashomer, Israel; Neufeld Cardiac Research Institute, Tel-Aviv University, Sheba Medical Center, Tel-Hashomer, Israel; Sheba Center for Regenerative Medicine, Stem Cell, and Tissue Engineering, Tel Hashomer, Israel.
  • Molotski N; Tamman Cardiovascular Research Institute, Sheba Medical Center, Tel-Hashomer, Israel; Neufeld Cardiac Research Institute, Tel-Aviv University, Sheba Medical Center, Tel-Hashomer, Israel; Sheba Center for Regenerative Medicine, Stem Cell, and Tissue Engineering, Tel Hashomer, Israel.
  • Aviv V; Sheba Center for Regenerative Medicine, Stem Cell, and Tissue Engineering, Tel Hashomer, Israel.
  • Feinberg MS; Tamman Cardiovascular Research Institute, Sheba Medical Center, Tel-Hashomer, Israel; Neufeld Cardiac Research Institute, Tel-Aviv University, Sheba Medical Center, Tel-Hashomer, Israel.
  • Goitein O; Diagnostic Imaging Department, Sheba Medical Center, Tel-Hashomer, Israel.
  • Kushnir T; Diagnostic Imaging Department, Sheba Medical Center, Tel-Hashomer, Israel.
  • Konen E; Diagnostic Imaging Department, Sheba Medical Center, Tel-Hashomer, Israel.
  • Epstein FH; University of Virginia, Department of Biomedical Engineering, Charlottesville, VA, USA.
  • Yagil Y; Laboratory for Molecular Medicine and Israeli Rat Genome Center, Faculty of Health Sciences, Ben-Gurion University, Barzilai Medical Center Campus, Ashkelon, Israel.
  • Leor J; Tamman Cardiovascular Research Institute, Sheba Medical Center, Tel-Hashomer, Israel; Neufeld Cardiac Research Institute, Tel-Aviv University, Sheba Medical Center, Tel-Hashomer, Israel; Sheba Center for Regenerative Medicine, Stem Cell, and Tissue Engineering, Tel Hashomer, Israel. Electronic addre
Int J Cardiol ; 203: 381-95, 2016 Jan 15.
Article em En | MEDLINE | ID: mdl-26539962
BACKGROUND: Inflammation has been implicated in the initiation, progression and manifestation of hypertensive heart disease. We sought to determine the role of monocytes/macrophages in hypertension and pressure overload induced left ventricular (LV) remodeling. METHODS AND RESULTS: We used two models of LV hypertrophy (LVH). First, to induce hypertension and LVH, we fed Sabra salt-sensitive rats with a high-salt diet. The number of macrophages increased in the hypertensive hearts, peaking at 10 weeks after a high-salt diet. Surprisingly, macrophage depletion, by IV clodronate (CL) liposomes, inhibited the development of hypertension. Moreover, macrophage depletion reduced LVH by 17% (p<0.05), and reduced cardiac fibrosis by 75%, compared with controls (p=0.001). Second, to determine the role of macrophages in the development and progression of LVH, independent of high-salt diet, we depleted macrophages in mice subjected to transverse aortic constriction and pressure overload. Significantly, macrophage depletion, for 3 weeks, attenuated LVH: a 12% decrease in diastolic and 20% in systolic wall thickness (p<0.05), and a 13% in LV mass (p=0.04), compared with controls. Additionally, macrophage depletion reduced cardiac fibrosis by 80% (p=0.006). Finally, macrophage depletion down-regulated the expression of genes associated with cardiac remodeling and fibrosis: transforming growth factor beta-1 (by 80%) collagen type III alpha-1 (by 71%) and atrial natriuretic factor (by 86%). CONCLUSIONS: Macrophages mediate the development of hypertension, LVH, adverse cardiac remodeling, and fibrosis. Macrophages, therefore, should be considered as a therapeutic target to reduce the adverse consequences of hypertensive heart disease.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pressão Sanguínea / Função Ventricular Esquerda / Hipertrofia Ventricular Esquerda / Remodelação Ventricular / Macrófagos / Miocárdio Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Int J Cardiol Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Israel País de publicação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pressão Sanguínea / Função Ventricular Esquerda / Hipertrofia Ventricular Esquerda / Remodelação Ventricular / Macrófagos / Miocárdio Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Int J Cardiol Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Israel País de publicação: Holanda