Next Article in Journal
Apoptosis Induction of Agave lechuguilla Torrey Extract on Human Lung Adenocarcinoma Cells (SK-LU-1)
Next Article in Special Issue
TRIMming down to TRIM37: Relevance to Inflammation, Cardiovascular Disorders, and Cancer in MULIBREY Nanism
Previous Article in Journal
Blood Outgrowth and Proliferation of Endothelial Colony Forming Cells are Related to Markers of Disease Severity in Patients with Pulmonary Arterial Hypertension
Open AccessReview

Novel Insights into the Crosstalk between Mineralocorticoid Receptor and G Protein-Coupled Receptors in Heart Adverse Remodeling and Disease

1
Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences (Pharmacology), College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA
2
Present address: Jackson Memorial Hospital, Miami, FL 33136, USA
3
Present address: Massachusetts General Hospital, Boston, MA 02114, USA
*
Author to whom correspondence should be addressed.
American Foundation for Pharmaceutical Education (AFPE) “Gateway to Research” Scholar.
Int. J. Mol. Sci. 2018, 19(12), 3764; https://doi.org/10.3390/ijms19123764
Received: 8 November 2018 / Revised: 21 November 2018 / Accepted: 23 November 2018 / Published: 27 November 2018
(This article belongs to the Special Issue Mechanisms of Inflammation in Degenerative Cardiovascular Conditions)
The mineralocorticoid hormone aldosterone regulates sodium and potassium homeostasis but also adversely modulates the maladaptive process of cardiac adverse remodeling post-myocardial infarction. Through activation of its mineralocorticoid receptor (MR), a classic steroid hormone receptor/transcription factor, aldosterone promotes inflammation and fibrosis of the heart, the vasculature, and the kidneys. This is why MR antagonists reduce morbidity and mortality of heart disease patients and are part of the mainstay pharmacotherapy of advanced human heart failure. A plethora of animal studies using cell type–specific targeting of the MR gene have established the importance of MR signaling and function in cardiac myocytes, vascular endothelial and smooth muscle cells, renal cells, and macrophages. In terms of its signaling properties, the MR is distinct from nuclear receptors in that it has, in reality, two physiological hormonal agonists: not only aldosterone but also cortisol. In fact, in several tissues, including in the myocardium, cortisol is the primary hormone activating the MR. There is a considerable amount of evidence indicating that the effects of the MR in each tissue expressing it depend on tissue- and ligand-specific engagement of molecular co-regulators that either activate or suppress its transcriptional activity. Identification of these co-regulators for every ligand that interacts with the MR in the heart (and in other tissues) is of utmost importance therapeutically, since it can not only help elucidate fully the pathophysiological ramifications of the cardiac MR’s actions, but also help design and develop novel better MR antagonist drugs for heart disease therapy. Among the various proteins the MR interacts with are molecules involved in cardiac G protein-coupled receptor (GPCR) signaling. This results in a significant amount of crosstalk between GPCRs and the MR, which can affect the latter’s activity dramatically in the heart and in other cardiovascular tissues. This review summarizes the current experimental evidence for this GPCR-MR crosstalk in the heart and discusses its pathophysiological implications for cardiac adverse remodeling as well as for heart disease therapy. Novel findings revealing non-conventional roles of GPCR signaling molecules, specifically of GPCR-kinase (GRK)-5, in cardiac MR regulation are also highlighted. View Full-Text
Keywords: adverse remodeling; aldosterone; cardiac myocyte; crosstalk; G protein-coupled receptor (GPCR); GPCR-kinase (GRK); heart failure; inflammation; mineralocorticoid receptor; myocardial infarction; oxidative stress; signal transduction adverse remodeling; aldosterone; cardiac myocyte; crosstalk; G protein-coupled receptor (GPCR); GPCR-kinase (GRK); heart failure; inflammation; mineralocorticoid receptor; myocardial infarction; oxidative stress; signal transduction
Show Figures

Figure 1

MDPI and ACS Style

Parker, B.M.; Wertz, S.L.; Pollard, C.M.; Desimine, V.L.; Maning, J.; McCrink, K.A.; Lymperopoulos, A. Novel Insights into the Crosstalk between Mineralocorticoid Receptor and G Protein-Coupled Receptors in Heart Adverse Remodeling and Disease. Int. J. Mol. Sci. 2018, 19, 3764.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map

1
Back to TopTop