Macrophages dictate the progression and manifestation of hypertensive heart disease
| Autor: | Jonathan Leor, Natalie Landa, Orly Goitein, Yoram Yagil, Tammar Kushnir, Micha S. Feinberg, Nili Naftali-Shani, Vered Aviv, David Kain, Fredrik H. Epstein, Eli Konen, Natali Molotski, Chana Yagil, Uri Amit |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Pathology Cardiac fibrosis Diastole Inflammation Blood Pressure 030204 cardiovascular system & hematology Ventricular Function Left Muscle hypertrophy 03 medical and health sciences 0302 clinical medicine Fibrosis Internal medicine Rats Inbred SHR medicine Macrophage Animals cardiovascular diseases Pressure overload Ventricular Remodeling business.industry Macrophages Myocardium medicine.disease Hypertensive heart disease Rats Disease Models Animal 030104 developmental biology Endocrinology Disease Progression Hypertrophy Left Ventricular medicine.symptom Cardiology and Cardiovascular Medicine business |
| Zdroj: | International journal of cardiology. 203 |
| ISSN: | 1874-1754 |
| Popis: | 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.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% (p0.05), 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 (p0.05), 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%).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. |
| Databáze: | OpenAIRE |
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