Loss of ABCA function is not only due to
Loss of ABCA1 function is not only due to its mutations, which is rare, and the use of CsA, which is gradually replaced by other immunosuppressive drugs, but is also caused by reduced expression in aging macrophages . The present study for the first time shows that the expression of ABCA1 in the principal Filipin Complex of aging mouse CCD is reduced and that the intracellular Cho is consistently increased in these aging cells. An age-related increase in Cho accumulation was also found in the mouse kidney . In parallel, our data show that ENaC activity and apical density are also elevated in kidney CCD. Unlike the elevated ENaC activity induced by pharmacological concentration of CsA, which presumably completely blocks ABCA1 function, the elevation of ENaC activity caused by reduced ABCA1 expression can be further increased by hypercholesterolemia, which is known to occur in ApoE KO mice on a high fat diet. It would be interesting to further investigate whether reduced ABCA1 expression participates in age-related hypertension and whether statins can prevent the development of hypertension in aging population.