Polymeric immunoglobulin receptor deficiency attenuates experimental atherosclerosis

Background Polymeric immunoglobulin receptor (PIGR) is a transmembrane protein widely expressed in mucosal epithelial cells that is involved in the transcytosis of the polymeric immunoglobulins IgA and IgM. Recent findings revealed increased plasma PIGR levels in subjects with subclinical atherosclerosis, although its function remains uncertain. Purpose To assess the role of PIGR in atherosclerosis. Methods We analyzed PIGR levels in human atherosclerotic plaques compared to healthy aortic samples, as well as in the serum of subjects with peripheral arterial disease (PAD) and controls. Next, we studied the effect of germline Pigr deficiency in experimental atherosclerosis ( Ldlr −/− /Pigr −/− mice fed a western-diet for 10 weeks). Circulating IgA and IgM levels, as well as B and T cell numbers in spleen and Peyer’s patches (PP), were analyzed by ELISA and flow cytometry, respectively. Results PIGR levels were increased in the intima of early human atherosclerotic lesions and in patients with PAD, compared to controls. Ldlr −/− /Pigr −/− mice showed elevated serum IgA and IgM levels, along with an increased number of germinal center B cells in both the spleen and PP. Moreover, Ldlr −/− /Pigr −/− mice displayed a significantly reduced plaque size in the aortic sinus and a strong decrease in foam cells (CD68 + ), while no changes were observed in contractile smooth muscle cells (α-actin + ) and collagen content compared to control Ldlr −/− mice. Conclusions Global Pigr deficiency decreases atherosclerosis, suggesting that PIGR blockade may have beneficial effects in vascular pathologies.