Raddatz MA, Huffstater T, Bersi MR, Reinfeld BI, Madden MZ, Booton SE, Rathmell WK, Rathmell JC, Lindman BR, Madhur MS, Merryman WD. Macrophages Promote Aortic Valve Cell Calcification and Alter STAT3 Splicing. Arteriosclerosis, thrombosis, and vascular biology. 2020 Dec;40(40). e153-e165. PMID: 32295422 [PubMed] PMCID: PMC7285853 NIHMSID: NIHMS1581976.
Macrophages have been described in calcific aortic valve disease, but it is unclear if they promote or counteract calcification. We aimed to determine how macrophages are involved in calcification using the model of calcific aortic valve disease. Approach and Results: Macrophages in wild-type and murine aortic valves were characterized by flow cytometry. Macrophages in aortic valves had increased expression of MHCII (major histocompatibility complex II). We then used bone marrow transplants to test if differences in macrophages drive disease. mice had increased valve thickness, macrophage infiltration, and proinflammatory macrophage maturation regardless of transplanted bone marrow genotype. In vitro approaches confirm that aortic valve cells promote macrophage invasion as quantified by migration index and proinflammatory phenotypes as quantified by Ly6C and CCR2 positivity independent of macrophage genotype. Finally, we found that macrophage interaction with aortic valve cells promotes osteogenic, but not dystrophic, calcification and decreases abundance of the STAT3β isoform.