期刊
HYPERTENSION
卷 54, 期 3, 页码 537-U180出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.109.131110
关键词
macrophages; monocytes; mineralocorticoid receptor; cardiac fibrosis; inflammation; tissue remodeling
资金
- National Health and Medical Research Council of Australia [388914]
- Monash Graduate Scholarship
Increased mineralocorticoid levels plus high salt promote vascular inflammation and cardiac tissue remodeling. Mineralocorticoid receptors are expressed in many cell types of the cardiovascular system, including monocytes/macrophages and other inflammatory cell types. Although mineralocorticoid receptors are expressed in monocytes/macrophages, their role in regulating macrophage function to date has not been investigated. We, thus, used the Cre/LoxP-recombination system to selectively delete mineralocorticoid receptors from monocytes/macrophages with the lysozyme M promoter used to drive Cre expression (MRflox/flox/LysM(Cre/-) mice). Male mice from each genotype (MRflox/flox or wild-type and MRflox/flox/LysM(Cre/-) mice) were uninephrectomized, given 0.9% NaCl solution to drink, and treated for 8 days or 8 weeks with either vehicle (n = 10) or deoxycorticosterone (n = 10). Equivalent tissue macrophage numbers were seen for deoxycorticosterone treatment of each genotype at 8 days; in contrast, plasminogen activator inhibitor type 1 and NAD(P) H oxidase subunit 2 levels were increased in wild-type but not in MRflox/flox/ LysM(Cre/-) mice given deoxycorticosterone. Baseline expression of other inflammatory genes was reduced in MRflox/flox/LysM(Cre/-) mice compared with wild-type mice. At 8 weeks, deoxycorticosterone-induced macrophage recruitment and connective tissue growth factor and plasminogen activator inhibitor type 1 mRNA levels were similar for each genotype; in contrast, MRflox/flox/LysM(Cre/-) mice showed no increase in cardiac fibrosis or blood pressure, as was seen in wild-type mice at 8 weeks. These data demonstrate the following points: (1) mineralocorticoid receptor signaling regulates basal monocyte/macrophage function; (2) macrophage recruitment is not altered by loss of mineralocorticoid receptor signaling in these cells; and (3) a novel and significant role is seen for macrophage signaling in the regulation of cardiac remodeling and systolic blood pressure in the deoxycorticosterone/salt model. (Hypertension. 2009; 54: 537-543.)
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