Alirocumab

Alirocumab is an anti-PCSK9 human monoclonal antibody. Alirocumab inhibits PCSK9. Alirocumab reduces NLRP3 inflammasome, regulates Nrf2/HO-1, HMGB1/NF-κB and Fractalkine/CX3CR1. Alirocumab increases the ability of the liver to bind LDL-cholesterol (LDL-C) and reduces levels of LDL-C in blood. Alirocumab improves atherosclerosis and inflammation^{[1][2][3][4][5][6][7][8][9][10][11]}. In Vitro:Alirocumab (40 μg/mL, 24 h) alleviates basal PCSK9 overexpression in vascular smooth muscle cells (VSMCs) of obese insulin-resistant Zucker rats (OZR)^[3].
Alirocumab (8 μg/mL, 72 h) attenuates Lp(a) secretion in primary human hepatocytes via inhibition of PCSK9^[4].
Alirocumab (10 μg/mL, 24 h) inhibits lipid-induced inflammation in HepG2 cells^[5].
In Vivo:Alirocumab (3-10 mg/kg, s.c., 18 weeks) inhibits atherosclerosis, improves the plaque morphology, and enhances the effects of a statin in APOE*3Leiden.CETP mice^[6].
Alirocumab (16 mg/kg/week, s.c., on day 0, day 7, and day 14) boosts antioxidant status and halts inflammation in rat model of sepsis-induced nephrotoxicity via modulation of Nrf2/HO-1, PCSK9/HMGB1/NF-ᴋB/NLRP3 and Fractalkine/CX3CR1 hubs^[7].
Alirocumab (50 mg/kg, s.c., weekly prior to exposure to the liquid diets) attenuates ethanol-induced neuronal injury in the brain and oxidative stress in rats^[8].
Alirocumab (1 mg/kg/week, s.c.) activates brown fat, increases hepatic uptake of cholesterol-rich TRL remnants, thereby lowering non-HDL-C, and increases HDL-C levels and cholesterol efflux capacity of HDL, further improving dyslipidemia in APOE*3-Leiden.CETP mice^[9].
Alirocumab (10 mg/kg, s.c., 2 weeks) reduces lipoprotein(a) levels in nonhuman primates by lowering apolipoprotein(a) production rate^[10].
Alirocumab (3-10 mg/kg, i.p., weekly for 16 weeks) reduces RAS, NLRP3 inflammasome, and cholecystokinin in lung tissue of obese mice^[11].