Propionyl-L-carnitine dilates human subcutaneous arteries through an endothelium-dependent mechanism

Cipolla, Marilyn J.; Nicoloff, Alexander D.; Rebello, Tessio; Amato, Anthony A.; Porter, John M.

doi:10.1016/s0741-5214(99)70251-x

Cited by 47 publications

(31 citation statements)

References 21 publications

(24 reference statements)

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“…Successively, an anti-ischemic effect of PLC on endothelial cells (42) and an endothelium-dependent vasodilatation in small intact arteries that vanishes in de-endothelialized ones have also been described (43). These pharmacological effects are confirmed from the improved walking capabilities in PLC-treated peripheral arterial disease patients (25,44).…”

Section: Discussionmentioning

confidence: 88%

Propionyl-L-carnitine Reduces Proliferation and Potentiates Bax-related Apoptosis of Aortic Intimal Smooth Muscle Cells by Modulating Nuclear Factor-κB Activity

Orlandi

Francesconi

Marcellini

et al. 2007

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 88%

Propionyl-L-carnitine Reduces Proliferation and Potentiates Bax-related Apoptosis of Aortic Intimal Smooth Muscle Cells by Modulating Nuclear Factor-κB Activity

Orlandi

Francesconi

Marcellini

et al. 2007

Journal of Biological Chemistry

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“…PLC-induced dilative adaptation confirms previous ex vivo experiments using subcutaneous arteries. 24 Moreover, PLC effects were found to be associated with increased endothelial cell proliferation but not SMC growth. These findings strongly suggest that endothelium is target for the pharmacological action of PLC.…”

Section: Discussionmentioning

confidence: 98%

Propionyl- l -Carnitine Improves Postischemic Blood Flow Recovery and Arteriogenetic Revascularization and Reduces Endothelial NADPH-Oxidase 4–Mediated Superoxide Production

Stasi

Scioli

Arcuri

et al. 2010

ATVB

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Objective-The beneficial effect of the natural compound propionyl-L-carnitine (PLC) on intermittent claudication in patients with peripheral arterial disease is attributed to its anaplerotic function in ischemic tissues, but inadequate information is available concerning action on the vasculature. Methods and Results-We investigated the effects of PLC in rabbit hind limb collateral vessels after femoral artery excision, mouse dorsal air pouch, chicken chorioallantoic membrane, and vascular cells by angiographic, Doppler flow, and histomorphometrical and biomolecular analyses. PLC injection accelerated hind limb blood flow recovery after 4 days (PϽ0.05) and increased angiographic quadriceps collateral vascularization after 7 days (PϽ0.001) Histomorphometry confirmed the increased vascular area (PϽ0.05), with unchanged intramuscular capillary density. PLCinduced dilatative adaptation, and growth was found associated with increased inducible nitric oxide synthase and reduced arterial vascular endothelial growth factor and intracellular adhesion molecule-1 expression. PLC also increased vascularization in air pouch and chorioallantoic membrane (PϽ0.05), particularly in large vessels. PLC increased endothelial and human umbilical vascular endothelial cell proliferation and rapidly reduced inducible nitric oxide synthase and NADPH-oxidase 4 -mediated reactive oxygen species production in human umbilical vascular endothelial cells; NADPH-oxidase 4 also regulated NF-B-independent intracellular adhesion molecule-1 expression. Conclusion-Our results provided strong evidence that PLC improves postischemic flow recovery and revascularization and reduces endothelial NADPH-oxidase-related superoxide production. We recommend that PLC should be included among therapeutic interventions that target endothelial function. Key Words: arteriogenesis Ⅲ endothelial function Ⅲ oxidative stress Ⅲ vascular function P eripheral arterial disease (PAD) is the most common clinical consequence of atherosclerosis, affecting Ϸ20% of adults older than age 55 years. 1 Atherosclerotic occlusion of leg arteries induces clinical manifestations, most frequently intermittent claudication. 1,2 Among the functional vascular changes observed with atherosclerosis, endothelial dysfunction plays a major role. 3,4 L-carnitine is a natural amino acid that plays a crucial role in the shuttle mechanism of long-chain fatty acids and in fueling ␤ oxidation. 5 The endogenous L-carnitine pool includes a series of short-chain, medium-chain, and long-chain esters in homeostatic equilibrium. 5,6 Propionyl-L-carnitine (PLC) is a short-chain L-carnitine ester that has been introduced among emerging noninterventional medical regiments that aim to counteract PAD-related adverse effects. 1,2,7 PLC activity is classically related to the anaplerotic function of providing substrates for energy expenditure in ischemic tissues. 1,8 Although some data showed beneficial remodeling after injury, 9 the mechanisms through which PLC influences arterial function remain largely hypot...

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“…Both LC and PLC are able to induce endothelium-dependent relaxation. The former enhances NO production in the aorta from hypertensive rats [1] and the latter promotes prostaglandin synthesis in subcutaneous human arteries [2]. Furthermore, we have recently reported that both compounds improved endothelial dysfunction in aortic rings from spontaneously hypertensive rats (SHR) by increasing NO participation in endothelium-dependent relaxations.…”

Section: Introductionmentioning

confidence: 99%

Effect of <i>L</i>-Carnitine and Propionyl-<i>L</i>-Carnitine on Endothelial Function of Small Mesenteric Arteries from SHR

et al. 2007

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Background:The effect of treatment with either 200 mg·kg^–1 of L-carnitine (LC) or propionyl-L-carnitine (PLC) was studied on endothelial dysfunction of small mesenteric arteries (SMA) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Methods: Systolic blood pressure (SBP) was measured and endothelial and vascular functions were assessed by the effect of carbachol (CCh) and phenylephrine (Phe). O₂^– produced by SMA and eNOS expression were evaluated by chemiluminescence and Western blot, respectively. Results: Although SBP was not affected, endothelial relaxation increased in both LC- and PLC-treated SHR. Nevertheless, the CCh-induced contraction remained sensitive to indomethacin in these rats. On the contrary, NO participation was increased in all the groups except for LC-treated WKY. Furthermore, high concentrations of Phe produced NO-dependent relaxation of SMA from PLC-treated rats. Both compounds decreased basal and NADPH-stimulated O₂^– in SHR toward values observed in WKY. Only PLC increased eNOS protein expression in SHR. Neither LC nor PLC affected endothelium-derived hyperpolarizing factor-induced relaxation. Conclusions: LC and its propionate improved endothelial responses of SMA from SHR by decreasing O₂^– production and thus increasing NO availability. PLC also increased NO synthesis by enhancing eNOS expression.

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Propionyl-L-carnitine dilates human subcutaneous arteries through an endothelium-dependent mechanism

Abstract: PLC is an endothelium-dependent vasodilator, the mechanism of which is partially mediated by prostaglandin synthesis, not nitric oxide. The beneficial effects of this compound may, in part, be related to vasodilation and enhanced blood flow.

Cited by 47 publications

References 21 publications

Propionyl-L-carnitine Reduces Proliferation and Potentiates Bax-related Apoptosis of Aortic Intimal Smooth Muscle Cells by Modulating Nuclear Factor-κB Activity

Propionyl-L-carnitine Reduces Proliferation and Potentiates Bax-related Apoptosis of Aortic Intimal Smooth Muscle Cells by Modulating Nuclear Factor-κB Activity

Propionyl- l -Carnitine Improves Postischemic Blood Flow Recovery and Arteriogenetic Revascularization and Reduces Endothelial NADPH-Oxidase 4–Mediated Superoxide Production

Effect of <i>L</i>-Carnitine and Propionyl-<i>L</i>-Carnitine on Endothelial Function of Small Mesenteric Arteries from SHR

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