Abstract 11515: Mannose-Binding Lectin is Dysregulated in Cardiac Endothelial Cells of Women With Peripartum Cardiomyopathy

• Published in: Circulation (New York, N.Y.) Vol. 146; no. Suppl_1; p. A11515
• Main Authors: Aryan, Zahra, Moghadami, Siavash, Wang, Wei, Sadoshima, Junichi
• Format: Journal Article
• Language: English
• Published: Lippincott Williams & Wilkins 08-11-2022
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.146.suppl_1.11515

IntroductionPeripartum cardiomyopathy (PPCM) is a type of heart failure that presents with systolic dysfunction in the third trimester of pregnancy or early postpartum. Viral myocarditis, genetic predisposition, and hormonal changes are suggested as contributing factors to PPCM. However, the molecular basis of PPCM remained elusive. HypothesisCardiac expression of genes involved in immune system response is dysregulated in PPCM. MethodsWe identified women with PPCM and age/race-matched heart donors from a dataset obtained from Myocardial Applied Genomics Network (MAGNet) consortium. Left ventricular (LV) biopsies were taken at the time of heart transplantation. Bulk RNA-seq was performed on LV tissue of patients with PPCM and non-failing heart donors (NF). We used the Human Cell Atlas (HCA) reference database with accession code ERP128138 to investigate cell-specific enrichment of genes. ResultsMean age of study participants was 36.1 years and 33.3% of participants had African American ancestry. We found that LCN6 (Log2(fold_change) = -4.1, p-val = 0.0027) and FCN3 (Log2(fold_change) = -3.4, p-val = 0.0042) are downregulated in LV tissue obtained from PPCM compared to NF. LCN6 encodes lipocalin-6 and FCN3 encodes ficolin-3 which are upstream of the mannose-binding lectin complement pathway. Based on HCA dataset on adult human hearts, we observed that LCN6 and FCN3 genes are mainly expressed by endothelial cells. ConclusionsWe demonstrated that expression of LCN6 and FCN3 genes, which are upstream of the mannose-binding lectin pathway, is decreased in cardiac endothelial cells of individuals with PPCM. Mannose-binding lectin is a soluble pattern recognition receptor that identifies mannose and N-acetylglucosamine residues in a wide variety of pathogens and antigen-antibody complexes and works as an opsonin that facilitates phagocytosis. Our findings suggest the possibility of impaired immune complex clearance in PPCM pathogenesis.