Details

Autor(en) / Beteiligte

• 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

Titel

Macrophages dictate the progression and manifestation of hypertensive heart disease

Ist Teil von

• International journal of cardiology, 2016-01, Vol.203, p.381-395

Ort / Verlag

Netherlands: Elsevier Ireland Ltd

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• ABSTRACT 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.