CXCR4 and heart failure: Elevated CXCL12 associates with coronary artery disease and heart-failure risk, yet CXCR4 signaling in B cells often appears atheroprotective—supporting retention and migration into bone-marrow and PVAT niches that favor natural IgM production.[29, 42, 77] Paradoxically, CXCR4, the main receptor for CXCL12, often exerts atheroprotective effects [28].