Macrophage Mineralocorticoid Receptor Is a Pleiotropic Modulator of Myocardial Infarct Healing

Abstract

Supplemental Digital Content is available in the text.

Vascular and inflammatory mineralocorticoid receptors in kidney disease

“…54 Persistent infiltration of inflammatory cells and macrophages plays an essential role during the repair process after ischaemic AKI. [34][35][36][37][38][39][40] Thus, we showed that infiltrating macrophages display increased M2-polarization markers in mice lacking the MR in the myeloid lineage and subjected to bilateral renal IR and that the population of pro-inflammatory Ly6C high macrophages is smaller than that of control littermates. 55,56 As already highlighted, we and others have shown that the MR in macrophages plays a key role in classical M1 polarization, whereas MR deficiency or blockade favours M2 polarization.…”

“…55,56 As already highlighted, we and others have shown that the MR in macrophages plays a key role in classical M1 polarization, whereas MR deficiency or blockade favours M2 polarization. [34][35][36][37][38][39][40] Thus, we showed that infiltrating macrophages display increased M2-polarization markers in mice lacking the MR in the myeloid lineage and subjected to bilateral renal IR and that the population of pro-inflammatory Ly6C high macrophages is smaller than that of control littermates. This effect was associated with the prevention of kidney fibrosis and the AKI-to-CKD transition.…”

“…34 Transgenic mice have also been a valuable tool to explore the role of the MR in macrophage activation. 40 This evidence shows that the MR is a crucial factor that modulates the polarization/differentiation of macrophages. Indeed, myeloid MR knockout (KO) mice are protected against cardiac injury induced by L-NAME angiotensin II hypertension.…”

“…36 Moreover, the same pattern of M2 macrophage polarization after MR inhibition has been reported in other pathological situations, such as cerebral ischaemia, 37 cardiac hypertrophy induced by aortic constriction, 38 central nervous system auto-immunity 39 and myocardial infarct healing. 40 This evidence shows that the MR is a crucial factor that modulates the polarization/differentiation of macrophages. However, the migration capacity of macrophages appears to be unaffected by MR deficiency.…”

Figures of the Heart Failure Association: Professor Dr. med. Johann Bauersachs, Chair of the Clinical Science Section

“…This paper was the first to demonstrate that MR activation in the heart is an essential driver of cardiac remodelling and inferred that MR antagonism considerably affects the heart independently of renal actions. The seminal contributions of two postdocs in my lab, Drs Daniela Fraccarollo and Paolo Galuppo, to the studies on aldosterone/MR for more than 20 years also lead to a recent important publication: using cell specific deletion of the MR in macrophages, we could decipher its decisive role for the modulation of myocardial infarct healing.…”