Early Atheroma-Derived Agonists of Peroxisome Proliferator–Activated Receptor-γ Trigger Intramedial Angiogenesis in a Smooth Muscle Cell–Dependent Manner

Pathology of human plaque vulnerability: Mechanisms and consequences of intraplaque haemorrhages

“…So what could be the topological mechanism relating initial lipid retention to the development of inwardly sprouting adventitial vessels directed towards the lipid-rich intima? We hypothesized that the mechanism of neo-angiogenesis is lipid-dependent, and that intimal-borne lipid mediators are able to induce centripetal neo-angiogenesis [36]. Our observations showed that this process involves first the outward convection of lipids, from the intima across the media, able to stimulate the VSMC PPARg receptors.…”

Pancreatic Cancer-Induced Neutrophil Extracellular Traps: A Potential Contributor to Cancer-Associated Thrombosis

“…The protein and lipid fractions were separated as described previously with slight modifications [59]. Briefly, conditioned media were mixed with 100% butanol (1:2) and vortexed before incubating at 4 °C for 90 min.…”

PPAR-γ as a therapeutic target in cardiovascular disease: evidence and uncertainty

“…In rabbits with atherosclerosis induced by highcholesterol diet and balloon arterial injury, 3 months of treatment with pioglitazone reduced lesion infl ammation, as gauged noninvasively by 18 F-deoxyglucose positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging and pathologically by lesion macrophage density and neovascularization ( 125 ). However, a study of advanced atherosclerotic lesions in LDL-receptor knockout mice showed that TZD drugs promoted plaque necrosis ( 27 ), and a recent study determined that atheromatous human aortas are enriched in soluble lipid mediators that may induce neovascularization of the arterial wall through a PPAR-␥ dependent mechanism ( 28 ). Clinically, such effects might predispose to plaque hemorrhage and rupture.…”

“…Several large trials in patients with type 2 diabetes found no signifi cant difference in cardiovascular morbidity and mortality among patients treated with more intensive or less intensive glycemic control regimens PPAR-␥ activators may increase concentrations of low density lipoprotein cholesterol (LDL-C) ( 23 ); and in vitro and animal studies suggest that thiazolidinedione (TZD) PPAR-␥ activators may interact with cardiac ion channels to promote arrhythmias (24)(25)(26). While some studies have shown that PPAR-␥ activation retards atherosclerosis ( 18 ), others have indicated a greater propensity for plaque necrosis ( 27,28 ). Thus, the net balance of favorable and unfavorable effects of PPAR-␥ activation on cardiovascular outcomes remains uncertain ( Table 1 ).…”