Increased hydrolysis of cholesteryl ester with prostacyclin is potentiated by high density lipoprotein through the prostacyclin stabilization.

Abstract

Prostacyclin (PGI2) has been reported to stimulate activities of acid cholesteryl ester hydrolase (ACEH; EC 3.1.1.13) and neutral cholesteryl ester hydrolase (NCEH; EC 3.1.1.13) in the smooth muscle cells leading to a decrease in intracellular cholesteryl ester. Recently, we have found that the half-life of PGI2 was prolonged through stabilization by HDL. HDL is known to have anti-atherogenic properties, although its precise mechanism has not been fully clarified. We therefore hypothesized that HDL can exert anti-atherogenic action by augmenting PGI2-stimulated increases in the activities of ACEH and NCEH. After incubation with PGI2 and HDL, a cell homogenate was made from which the activities of ACEH and NCEH were assessed. HDL significantly augmented the PGI2-induced increase in the activities of both enzymes. This effect of HDL was abolished in the absence of PCI2. Elevated intracellular levels of cyclic AMP were maintained for longer periods by HDL. The increase in both intracellular cyclic AMP levels and enzyme activities disappeared in the presence of an inhibitor of adenylate cyclase, 2'5'-dideoxyadenosine. Radiolabeled smooth muscle cells demonstrated a significant loss in total cholesterol and cholesteryl ester after treatment with PGI2 and HDL, due to the increase in cholesteryl ester hydrolytic activities. These data suggest that HDL enhanced the PGI2-stimulated hydrolysis of cholesteryl ester and augmented the PG12-induced reduction of cellular cholesteryl ester content by stabilizing

Interactions Between Nitric Oxide and Prostacyclin

“…80 Apart from bovious antiatherosclerotic acute effects of PGI 2 , such as synergism with NO in antiplatelet and fibrinolytic actions, its pathophysiologic antagonism with TXA 2 and its "cytoprotective" action, there are also chronic effects of PGI 2 that are involved mainly with metabolism of cholesterol and lipoproteins. Firstly, PGE 1 decreases influx of low density lipoproteins (LDL) into arterial walls in vivo, 81 secondly PGI 2 through cyclic AMP stimulates cholesteryl ester hydrolysis within smooth muscle cells in vitro, 82 and this effect of PGI 2 is potentiated by high density lipoproteins (HDL) 83 through stabilization of PGI 2 by HDL. 84 In patients with myocardial infarction or unstable angina pectoris, the stabilization of PGI 2 by HDL-associated apolipoprotein A-1 is impaired.…”

“…84 In patients with myocardial infarction or unstable angina pectoris, the stabilization of PGI 2 by HDL-associated apolipoprotein A-1 is impaired. 84 In summary, PGI 2 fortified by NO 85 might serve as an antithrombotic and antiatherosclerotic shield because of its platelet-suppressant, fibrinolytic cytoprotective, 86 antiproliferative, 71,87 antidegenerative and cholesterol-clearing 82,83 properties. Angiotoxicity and atherogenicity of cholesterol oxides are partially explained by the inhibition of PGI 2 synthase.…”

Engineered high-density lipoprotein particles that chaperone bioactive lipid mediators to combat endothelial dysfunction and thromboinflammation

“…Recently, IP receptor activators were shown to suppress inflammation-induced vascular leak, likely due to the engagement of the cAMP/ EPAC/ Rap1 pathway. The lability of PGI 2 due to autohydrolysis is inhibited by HDL association (17). Indeed, we found that purified A1M nanodiscs can associate with Iloprost, a stable PGI 2 analog (42) (Figure 4A).…”

“…ApoA1 also enhances endothelial-derived nitric oxide (NO) secretion, which promotes blood flow(15, 16). In addition, HDL suppresses thrombosis by enhancing the activity of prostacyclin (PGI 2 ) and attenuation of tissue factor expression(15, 17, 18).…”

Designer high-density lipoprotein particles enhance endothelial barrier function and suppress inflammation

“…ApoA1 also enhances endothelial-derived nitric oxide (NO) secretion, which promotes blood flow ( 11 ). In addition, HDL suppresses thrombosis by enhancing the activity of prostacyclin (PGI 2 ) and attenuation of tissue factor expression ( 12 , 13 ).…”