Critical role of scavenger receptor-BI–expressing bone marrow–derived endothelial progenitor cells in the attenuation of allograft vasculopathy after human apo A-I transfer

High density lipoproteins and endothelial functions: mechanistic insights and alterations in cardiovascular disease

“…Of note, the authors did not observe an increase in circulating Flk1/Sca-1 double-positive cells and DiI-acLDL/ FITC-isolectin double-positive cells after ex vivo culture of spleen mononuclear cells after AdA-I transfer in mice transplanted with SR-BI-defi cient bone marrow, suggesting that expression of SR-BI in bone marrow is critical for EOC mobilization induced by HDL ( 166 ). Furthermore, the migratory capacity of bone marrow-derived EOC deficient in SR-BI in response to HDL was reduced as compared with EOCs containing SR-BI, and this was at least in part due to an impaired activation of ERKs and decreased NO production in SR-BI-defi cient EOCs ( 166 ). In vivo, SR-BI defi ciency in bone marrow abrogated the inhibitory effect of AdA-I transfer on allograft vasculopathy after paratopical transplantation of a common carotid artery of a female BALB/c donor mouse into the recipient male C57BL/6 mouse, which was paralleled by impaired endothelial regeneration and EOC incorporation in allografts ( 166 ).…”

“…Furthermore, the migratory capacity of bone marrow-derived EOC deficient in SR-BI in response to HDL was reduced as compared with EOCs containing SR-BI, and this was at least in part due to an impaired activation of ERKs and decreased NO production in SR-BI-defi cient EOCs ( 166 ). In vivo, SR-BI defi ciency in bone marrow abrogated the inhibitory effect of AdA-I transfer on allograft vasculopathy after paratopical transplantation of a common carotid artery of a female BALB/c donor mouse into the recipient male C57BL/6 mouse, which was paralleled by impaired endothelial regeneration and EOC incorporation in allografts ( 166 ). Besides increasing HDL levels by adenoviral human apoA-I transfer, intravenous infusion of reconstituted HDL has also been shown to increase the number of Sca-1 positive cells in the aortic endothelium of apoE-defi cient mice, supporting a role for HDL in promoting endothelial repair ( 167 ).…”

“…In addition, HDL causes PI3K-mediated upregulation of the Bcl-xL expression ( 16 ). Interestingly, HDL retained its anti-apoptotic activity after knockdown of eNOS using specifi c RNA interference or pharmacological inhibition using N (G)-nitro-L-arginine methyl ester (16), suggesting that HDL may exert its anti-spleen-derived EOCs after 4 and 7 days of ex vivo culture ( 166 ). Of note, the authors did not observe an increase in circulating Flk1/Sca-1 double-positive cells and DiI-acLDL/ FITC-isolectin double-positive cells after ex vivo culture of spleen mononuclear cells after AdA-I transfer in mice transplanted with SR-BI-defi cient bone marrow, suggesting that expression of SR-BI in bone marrow is critical for EOC mobilization induced by HDL ( 166 ).…”

“…Interestingly, HDL retained its anti-apoptotic activity after knockdown of eNOS using specifi c RNA interference or pharmacological inhibition using N (G)-nitro-L-arginine methyl ester (16), suggesting that HDL may exert its anti-spleen-derived EOCs after 4 and 7 days of ex vivo culture ( 166 ). Of note, the authors did not observe an increase in circulating Flk1/Sca-1 double-positive cells and DiI-acLDL/ FITC-isolectin double-positive cells after ex vivo culture of spleen mononuclear cells after AdA-I transfer in mice transplanted with SR-BI-defi cient bone marrow, suggesting that expression of SR-BI in bone marrow is critical for EOC mobilization induced by HDL ( 166 ). Furthermore, the migratory capacity of bone marrow-derived EOC deficient in SR-BI in response to HDL was reduced as compared with EOCs containing SR-BI, and this was at least in part due to an impaired activation of ERKs and decreased NO production in SR-BI-defi cient EOCs ( 166 ).…”

Therapeutic Potential of HDL in Cardioprotection and Tissue Repair

“…The effect of HDL on EPC number, function, and incorporation occurs via SR-BI (Feng et al 2009b). Since HDLs have been demonstrated to increase vascular endothelial growth factor (VEGF) production by early EPCs in vitro, HDLs may improve reendothelialisation by its effects on these circulating proangiogenic cells (Feng et al 2011).…”