Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice

Foam cells and the pathogenesis of kidney disease

“…The structural changes that are present have not led to progressive CKD, and so without further modification these mice cannot serve as good model systems for the combined CKD and ASCVD that is so lethal to patients with kidney disease. In efforts to overcome this deficiency, animal models of ASCVD such as ApoE −/− and LDLR −/− mice have been subjected to further modifications such as partial nephrectomy [33] or administration of a renal toxin such as adriamycin, or introduction of specific gene mutations in order to induce CKD in the setting of ASCVD that is already present in order to model the situation in humans with CKD [34■,35]. Recent examples of such modifications include the study of Tavori et al [35] which overexpressed variants of apoE specifically in macrophages in both ApoE −/− and combined ApoE −/− / LDLR −/− mice.…”

“…In efforts to overcome this deficiency, animal models of ASCVD such as ApoE −/− and LDLR −/− mice have been subjected to further modifications such as partial nephrectomy [33] or administration of a renal toxin such as adriamycin, or introduction of specific gene mutations in order to induce CKD in the setting of ASCVD that is already present in order to model the situation in humans with CKD [34■,35]. Recent examples of such modifications include the study of Tavori et al [35] which overexpressed variants of apoE specifically in macrophages in both ApoE −/− and combined ApoE −/− / LDLR −/− mice. This study found macrophage specific expression of a variant of ApoE (ApoE Sendai ) linked to the development of lipoprotein glomerulopathy in humans is protective against atherosclerosis but causes lesions of lipoprotein glomerulopathy to develop in combined ApoE −/− / LDLR −/− mice.…”

Macrophage apoAI protects against dyslipidemia-induced dermatitis and atherosclerosis without affecting HDL

“…The lentiviral vector was prepared and expanded in our laboratory as previously described ( 29 ). In short, the self-inactivating (SIN) lentiviral vector (pWPT-WRPE), envelope plasmid pMD2.G, and packaging plasmid pCMV ⌬ R8.91 were kindly provided by Dr. Dider Trono (Lausanne, Switzerland).…”

Apolipoprotein E–related glomerular disorders

“…11,12 It is important to elucidate these functions when considering the role of apoE in the renal lesions associated with macrophages. 13 ApoE-related glomerular diseases ApoE2 homozygote glomerulopathy. In 1974, Amatruda et al 14 detailed glomerular lesions with foam cells in a case of type III HLP.…”

“…In addition to these experiments, some studies have shown that macrophages produce a small amount of apoE, which is important for the suppression of hyperlipidemia and arteriosclerosis. [11][12][13] Interestingly, one of these studies showed that the expression of macrophages producing apoE Sendai in mice that received a bone marrow transplant protected against atherosclerosis while inducing LPG. 13 Collectively, these results indicate that macrophages play various roles in lipoprotein metabolism involving apoE, and that their hyperactivity or suppression can be an important factor in each different type of renal lipidosis.…”