Mechanisms of mineralocorticoid receptor-mediated cardiac fibrosis and vascular inflammation.
OBJECTIVE
This review addresses the growing area of cardiovascular mineralocorticoid responses and highlights recent work investigating the underlying mechanisms that regulate mineralocorticoid receptor activation and translate mineralocorticoid receptor signaling into cardiac inflammation and fibrosis.


RESULTS
Mineralocorticoid receptor activation has been shown to regulate numerous pathways, including the plasminogen activation system and angiotensin II signaling pathways, which encompass both genomic and nongenomic responses. Mineralocorticoid receptor activation has been demonstrated to result in increased tissue oxidative stress and vascular inflammation, while recent studies provide evidence for changes in tissue oxidative stress, in turn regulating mineralocorticoid receptor activation by alternate ligands. These studies suggest possible mechanisms for the protection afforded by mineralocorticoid receptor blockade in the RALES and EPHESUS trials where plasma aldosterone levels were low or normal.


CONCLUSIONS
Experimental models of cardiac fibrosis and clinical observations have established mineralocorticoid receptor activation as a key player in the initiation and progression of cardiovascular disease. Studies over the last 12 months address the mechanisms underlying mineralocorticoid receptor-mediated vascular inflammation and cardiac fibrosis and focus on oxidative stress, inflammation and early tissue remodeling, and describe an increasing range of tissue signaling pathways and novel mechanisms of mineralocorticoid receptor activation that contribute to the pathology of cardiac fibrosis.
Young
Morag J
MJ
Prince Henry's Institute of Medical Research, Clayton, Australia. Morag.young@princehenrys.org
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D005355:Fibrosis; D005786:Gene Expression Regulation; D006331:Heart Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006727:Hormone Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008024:Ligands; D000451:Mineralocorticoid Receptor Antagonists; D008901:Mineralocorticoids / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014657:Vasculitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020257:Ventricular Remodeling
D006727:Hormone Antagonists; D008024:Ligands; D000451:Mineralocorticoid Receptor Antagonists; D008901:Mineralocorticoids; D018161:Receptors, Mineralocorticoid; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2