Recombinant apolipoprotein A-IMilano dimer inhibits carotid intimal thickening in hypercholesterolemic rabbits

Recombinant apolipoprotein A-IMilano for the treatment of cardiovascular diseases

“…Three weeks later, sHDL-treated rabbits showed a reduced intimal thickening compared with placebo (-71%) and with PC-only treated rabbits (-57%) [27]. A similar reduction in neointima formation, together with a decrease in smooth muscle cell proliferation, was achieved when the same dosing schedule was applied to hypercholesterolemic rabbits undergoing vascular injury through perivascular manipulation [28]. The most striking demonstration of the therapeutic potential of A-I M /A-I M sHDL in the prevention of clinical restenosis comes from recent experiments in a porcine model of coronary stenting [29•].…”

“…Interestingly, sHDL was effective in inhibiting intimal thickening only when administered before injury; moreover, these effects were achieved without any significant changes in plasma and aortic cholesterol content [28]. These observations postulate a role for A-I M /A-I M sHDL in the early events of lesion formation, possibly by mechanisms additive to enhanced reverse cholesterol transport.…”

Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis

“…These promising findings indicate outperformance of typical reductions in plaque volume established after statin therapy, the most efficient approach at present to delay progression of atherosclerosis, e.g., 0.9% reduction after 18 months of intensive therapy with 80 mg of atorvastatin in the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study (Nissen et al, 2004;Birjmohun et al, 2005). In addition, apoA-I Milano-containing rHDL potently reduce atherosclerosis in atherosclerotic rabbits (Ameli et al, 1994;Soma et al, 1995) and mice (Shah et al, 1998(Shah et al, , 2001. The regression of atherosclerosis induced by rHDL is most probably related to accelerated cholesterol efflux from the arterial wall with enhanced RCT to the liver (Nissen et al, 2003); the mechanistic relevance of other antiatherosclerotic activities of HDL to plaque regression remains unclear.…”

Innovative pharmaceutical interventions in cardiovascular disease: Focusing on the contribution of non-HDL-C/LDL-C-lowering versus HDL-C-raisingA systematic review and meta-analysis of relevant preclinical studies and clinical trials

“…In these studies, the effects of niacin (Kuhnast et al, 2013;Parwaresch et al, 1978), PPAR-α agonists (Corti et al, 2007;Srivastava, 2011), PPAR α/γ agonist (van der Hoorn et al, 2009), CETP antisense (Sugano, 1998), CETP vaccines (Gaofu et al, 2005;Jun et al, 2012;Mao et al, 2006;Rittershaus et al, 2000), CETP inhibitors (de Haan et al, 2008a;Huang et al, 2002;Kuhnast et al, 2014b;Morehouse et al, 2007;Okamoto et al, 2000), SR-BI inhibitor (Masson et al, 2009), ABCA1 degradation inhibitors (Arakawa et al, 2009), purified or reconstituted HDL (Badimon et al, 1990;Mezdour et al, 1995;Miyazaki et al, 1995;Nicholls et al, 2005), apolipoprotein A-I Milano (Ameli et al, 1994;Chiesa, 2002;Ibanez et al, 2012;Ibanez et al, 2008;Parolini et al, 2008;Soma et al, 1995) and apolipoprotein A-I mimetic peptide (Iwata et al, 2011;Van Lenten et al, 2007) on atherosclerosis development were investigated in APOE*3Leiden.CETP and ldlr +/-.CETP mice, New Zealand White (NZW), Japanese White (JW) and Watanabe heritable hyperlipidemic (WHHL) rabbits, as well as F1B hamsters.…”