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

Orlandi, Augusto; Francesconi, Arianna; Marcellini, Marcella; Lascio, Antonio Di; Spagnoli, Luigi Giusto

doi:10.1074/jbc.m606148200

Cited by 32 publications

(46 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[ 3 H]thymidine incorporation, apoptosis, and cell viability were also determined. 17 Results were expressed as the mean of 3 different experiments.…”

Section: Cell Culturementioning

confidence: 99%

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

Self Cite

View full text Add to dashboard Cite

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...

show abstract

“…[ 3 H]thymidine incorporation, apoptosis, and cell viability were also determined. 17 Results were expressed as the mean of 3 different experiments.…”

Section: Cell Culturementioning

confidence: 99%

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, LC treatment (300 mg/kg body weight per day) for 7 and 14 d caused significant reduction of the tissue lipid peroxidation and marked improvement of the antioxidant status in atherosclerotic rats [41] , and the long-term oral administration of LC was associated with a decrease of plaque cell proliferation and the severity of aortic atherosclerotic lesions in a rabbit model [22] . Furthermore, previous data documented the fact that LC prevented the progression of atherosclerotic lesions in rabbits in association with a significant reduction of VSMC proliferation and plasma triglycerides [22][23][24][25] .…”

Section: Discussionmentioning

confidence: 99%

“…LC and TAU can exert therapeutic effects on atherosclerosis [14,[16][17][18][22][23][24][25] . Our present data indicate that LC and TAU synergistically inhibit the proliferation and β-GP-induced osteoblastic differentiation of VSMCs.…”

Section: Discussionmentioning

confidence: 99%

“…The conditions that appear to benefit from exogenous supplementation of LC include cardiovascular disease, anorexia, chronic fatigue, diphtheria, hypoglycemia, male infertility, muscular myopathies, Rett syndrome, dialysis, preterm infants and HIV-positive individuals [21] . Previous data documented that LC has a strong anti-atherogenic potential [22][23][24][25] .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

L-carnitine and taurine synergistically inhibit the proliferation and osteoblastic differentiation of vascular smooth muscle cells

et al. 2010

View full text Add to dashboard Cite

Aim: To investigate the synergistic action of L-carnitine (LC) and taurine (TAU) on the proliferation and osteoblastic differentiation of vascular smooth muscle cells (VSMCs). Methods: DNA and protein synthesis of VSMCs were assessed using scintillation counting. Alkaline phosphatase (ALP) activity and calcium content were determined to investigate the effects of LC and TAU on the osteoblastic differentiation and mineralization of VSMCs. TAU uptake by VSMCs was assayed. RNA interference was used to down-regulate the expression of the TAU transporter (TAUT) in rat VSMCs. Results: LC and TAU synergistically inhibited the proliferation and β-glycerophosphate (β-GP)-induced osteoblastic differentiation of VSMCs as evidenced by the decreased [ 3 H]thymidine incorporation, ALP activity and calcium deposition. Furthermore, LC stimulated the TAU uptake and TAUT expression in VSMCs. Suppression of TAUT with short hairpin RNA (shRNA) abolished the synergistic action of LC and TAU in VSMCs. Conclusion: The synergistic inhibitory action of LC and TAU on the proliferation and osteoblastic differentiation of VSMCs is attributable to the up-regulation of TAUT expression and TAU uptake by LC.

show abstract

“…To investigate tumor apoptosis, rehydrated sections were stripped from proteins through incubation with 300 units/mL proteinase K (Sigma-Aldrich) for 15 min at 37jC, apoptotic nuclei were revealed by TUNEL, and the TUNEL labeling index (positive nuclei per mm 2 ) was calculated as reported previously (23).…”

Section: Histologic Examinationsmentioning

confidence: 99%

Preclinical profile of antitumor activity of a novel hydrophilic camptothecin, ST1968

Pisano

Cesare

Beretta

et al. 2008

Molecular Cancer Therapeutics

Self Cite

View full text Add to dashboard Cite

ST1968 is a novel hydrophilic camptothecin (CPT) derivative of the 7-oxyiminomethyl series. Because ST1968 retained ability to form remarkably stable cleavable complexes, this study was done to investigate its preclinical profile of antitumor activity in a large panel of human tumor models, including irinotecan-resistant tumors. Although less potent than SN38 in vitro, i.v. administered ST1968 caused a marked tumor inhibition, superior to that of irinotecan, in most tested models. ST1968 exhibited an impressive activity against several tumors including models of ovarian and colon carcinoma in which a high rate of cures was observed. In the most responsive tumors, complete and persistent tumor regressions were achieved even with low suboptimal doses. Even tumors derived from intrinsically resistant cells exhibited a significant responsiveness.

show abstract

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

Cited by 32 publications

References 59 publications

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

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

L-carnitine and taurine synergistically inhibit the proliferation and osteoblastic differentiation of vascular smooth muscle cells

Preclinical profile of antitumor activity of a novel hydrophilic camptothecin, ST1968

Contact Info

Product

Resources

About