Atrial Tissue Pro‐Fibrotic M2 Macrophage Marker CD163+, Gene Expression of Procollagen and B‐Type Natriuretic Peptide

Abstract

Background Atrial tissue fibrosis is linked to inflammatory cells, yet is incompletely understood. A growing body of literature associates peripheral blood levels of the antifibrotic hormone BNP (B‐type natriuretic peptide) with atrial fibrillation ( AF ). We investigated the relationship between pro‐fibrotic tissue M2 macrophage marker Cluster of Differentiation ( CD )163+, atrial procollagen expression, and BNP gene expression in patients with and without AF . Methods and Results In a cross‐sectional study design, right atrial tissue was procured from 37 consecutive, consenting, stable patients without heart failure or left ventricular systolic dysfunction, of whom 10 had AF and 27 were non‐ AF controls. Samples were analyzed for BNP and fibro‐inflammatory gene expression, as well as fibrosis and CD 163+. Primary analyses showed strong correlations (all P <0.008) between M2 macrophage CD 163+ staining, procollagen gene expression, and myocardial BNP gene expression across the entire cohort. In secondary analyses without multiplicity adjustments, AF patients had greater left atrial volume index, more valve disease, higher serum BNP , and altered collagen turnover markers versus controls (all P <0.05). AF patients also showed higher atrial tissue M2 macrophage CD 163+, collagen volume fraction, gene expression of procollagen 1 and 3, as well as reduced expression of the BNP clearance receptor NPRC (all P <0.05). Atrial procollagen 3 gene expression was correlated with fibrosis and BNP gene expression was correlated with serum BNP . Conclusions Elevated atrial tissue pro‐fibrotic M2 macrophage CD 163+ is associated with increased myocardial gene expression of procollagen and anti‐fibrotic BNP and is higher in patients with AF . More work on modulation of BNP signaling for treatment and prevention of AF may be warranted.

HIMF deletion ameliorates acute myocardial ischemic injury by promoting macrophage transformation to reparative subtype

“…These data collectively indicate the critical role of HIMF in promoting macrophage polarization into the M1-like subgroup, exaggerating the inflammatory response and tissue damage post MI. Of note, this M2-like transition had negligible effects on anti-inflammatory M2 marker genes, such as IL-10, CX3CR1; and the function of CD163 + M2 macrophage in MI heart is currently elusive, especially considering quite distinct roles in the context of different diseases and conditions [ 9 , 12 , 34 , 42 ]. Here, we can only speculate that an Himf deficiency likely tunes macrophages to exhibit a more reparative-prone status mainly by upregulating Arg1 expression.…”

Small-Molecule Integrated Stress Response Inhibitor Reduces Susceptibility to Postinfarct Atrial Fibrillation in Rats via the Inhibition of Integrated Stress Responses

“…The atrial inflammation mediates electrical and structural remodeling, and modulates calcium homeostasis and gap junction (Hu et al, 2015;Packer, 2020). Patients with AF have an increased immune cell infiltration in the atria, such as CD45 + lymphocytes, CD68 + macrophages (Chen et al, 2008), CD163 + macrophages (Watson et al, 2020), and This article has not been copyedited and formatted. The final version may differ from this version.…”

“…CD163-positive macrophages have been known as a marker of M2 subtype (Liu et al, 2019), also have potential pro-fibrotic role in atrium from AF (Watson et al, 2020). Thus, the ISR plays an important role in regulating atrial proinflammatory response.…”

Identification of Key Genes and Pathways in Hypertrophic Cardiomyopathy via Weighted Gene Co-Expression Network Analysis

“…The upregulated expression of this receptor re ects the switch of macrophage to activated phenotypes in in ammation and thus, a high CD163 expression in macrophages re ects the activated response of tissues to in ammation [40]. Enhanced expression of CD163+ or soluble CD163+ macrophages were detected in human in ammatory diseases including chronic cardiovascular disease like atherosclerosis [41], atrial brillation [42,43], and chronic heart failure [44,45]. Therefore, novel evidence indicated CD163 a potential in ammation biomarker and a therapeutic target in a large spectrum of acute and chronic in ammatory disorders [46,47].…”