Limits...
Propionyl-L-Carnitine Enhances Wound Healing and Counteracts Microvascular Endothelial Cell Dysfunction.

Scioli MG, Lo Giudice P, Bielli A, Tarallo V, De Rosa A, De Falco S, Orlandi A - PLoS ONE (2015)

Bottom Line: A daily oral PLC treatment improved skin flap viability and associated with reactive oxygen species (ROS) reduction, inducible nitric oxide synthase (iNOS) and NO up-regulation, accelerated wound healing and increased capillary density, likely favoring dermal angiogenesis by up-regulation for iNOS, vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and reduction of NADPH-oxidase 4 (Nox4) expression.Interestingly, inhibition of β-oxidation counteracted the beneficial effects of PLC on oxidative stress and endothelial dysfunction.The beneficial effects of PLC likely derived from improvement of mitochondrial β-oxidation and reduction of Nox4-mediated oxidative stress and endothelial dysfunction.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedicine and Prevention, Anatomic Pathology, University of Tor Vergata, Rome, Italy.

ABSTRACT

Background: Impaired wound healing represents a high cost for health care systems. Endothelial dysfunction characterizes dermal microangiopathy and contributes to delayed wound healing and chronic ulcers. Endothelial dysfunction impairs cutaneous microvascular blood flow by inducing an imbalance between vasorelaxation and vasoconstriction as a consequence of reduced nitric oxide (NO) production and the increase of oxidative stress and inflammation. Propionyl-L-carnitine (PLC) is a natural derivative of carnitine that has been reported to ameliorate post-ischemic blood flow recovery.

Methods and results: We investigated the effects of PLC in rat skin flap and cutaneous wound healing. A daily oral PLC treatment improved skin flap viability and associated with reactive oxygen species (ROS) reduction, inducible nitric oxide synthase (iNOS) and NO up-regulation, accelerated wound healing and increased capillary density, likely favoring dermal angiogenesis by up-regulation for iNOS, vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and reduction of NADPH-oxidase 4 (Nox4) expression. In serum-deprived human dermal microvascular endothelial cell cultures, PLC ameliorated endothelial dysfunction by increasing iNOS, PlGF, VEGF receptors 1 and 2 expression and NO level. In addition, PLC counteracted serum deprivation-induced impairment of mitochondrial β-oxidation, Nox4 and cellular adhesion molecule (CAM) expression, ROS generation and leukocyte adhesion. Moreover, dermal microvascular endothelial cell dysfunction was prevented by Nox4 inhibition. Interestingly, inhibition of β-oxidation counteracted the beneficial effects of PLC on oxidative stress and endothelial dysfunction.

Conclusion: PLC treatment improved rat skin flap viability, accelerated wound healing and dermal angiogenesis. The beneficial effects of PLC likely derived from improvement of mitochondrial β-oxidation and reduction of Nox4-mediated oxidative stress and endothelial dysfunction. Antioxidant therapy and pharmacological targeting of endothelial dysfunction may represent a promising tool for the treatment of delayed wound healing or chronic ulcers.

No MeSH data available.


Related in: MedlinePlus

PLC reduces oxidative stress in serum-deprived HMVECs.(A) Real-time PCR for Nox4 transcripts in serum-deprived PBS-treated (vehicle) or PLC-treated HMVECs at different times. (B) ROS level detection by dichlorodihydrofluorescein fluorescence intensity (DCF F.I). (C) FAD level (β-oxidation impairment) measured as optical density (OD) assay. t-Student: * and ** indicate p< 0.05 and p< 0.01, respectively. Values are expressed as mean ± SEM of three separate experiments. Abbreviations: OD, optical density.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4608702&req=5

pone.0140697.g006: PLC reduces oxidative stress in serum-deprived HMVECs.(A) Real-time PCR for Nox4 transcripts in serum-deprived PBS-treated (vehicle) or PLC-treated HMVECs at different times. (B) ROS level detection by dichlorodihydrofluorescein fluorescence intensity (DCF F.I). (C) FAD level (β-oxidation impairment) measured as optical density (OD) assay. t-Student: * and ** indicate p< 0.05 and p< 0.01, respectively. Values are expressed as mean ± SEM of three separate experiments. Abbreviations: OD, optical density.

Mentions: In HMVEC cultures, PLC treatment counteracted serum deprivation-induced oxidative stress and mitochondrial impairment, associated with endothelial dysfunction. In particular, PLC reduced Nox4 expression and ROS generation (Fig 6A and 6B). Moreover, as shown in Fig 6C, serum deprivation also determined a time-dependent increase of FAD level, indicating an impairment of β-oxidation and mitochondrial function; PLC treatment counteracted the impairment of β-oxidation. Similar findings were also documented in PLC-treated HUVEC cultures (S2 Fig).


Propionyl-L-Carnitine Enhances Wound Healing and Counteracts Microvascular Endothelial Cell Dysfunction.

Scioli MG, Lo Giudice P, Bielli A, Tarallo V, De Rosa A, De Falco S, Orlandi A - PLoS ONE (2015)

PLC reduces oxidative stress in serum-deprived HMVECs.(A) Real-time PCR for Nox4 transcripts in serum-deprived PBS-treated (vehicle) or PLC-treated HMVECs at different times. (B) ROS level detection by dichlorodihydrofluorescein fluorescence intensity (DCF F.I). (C) FAD level (β-oxidation impairment) measured as optical density (OD) assay. t-Student: * and ** indicate p< 0.05 and p< 0.01, respectively. Values are expressed as mean ± SEM of three separate experiments. Abbreviations: OD, optical density.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608702&req=5

pone.0140697.g006: PLC reduces oxidative stress in serum-deprived HMVECs.(A) Real-time PCR for Nox4 transcripts in serum-deprived PBS-treated (vehicle) or PLC-treated HMVECs at different times. (B) ROS level detection by dichlorodihydrofluorescein fluorescence intensity (DCF F.I). (C) FAD level (β-oxidation impairment) measured as optical density (OD) assay. t-Student: * and ** indicate p< 0.05 and p< 0.01, respectively. Values are expressed as mean ± SEM of three separate experiments. Abbreviations: OD, optical density.
Mentions: In HMVEC cultures, PLC treatment counteracted serum deprivation-induced oxidative stress and mitochondrial impairment, associated with endothelial dysfunction. In particular, PLC reduced Nox4 expression and ROS generation (Fig 6A and 6B). Moreover, as shown in Fig 6C, serum deprivation also determined a time-dependent increase of FAD level, indicating an impairment of β-oxidation and mitochondrial function; PLC treatment counteracted the impairment of β-oxidation. Similar findings were also documented in PLC-treated HUVEC cultures (S2 Fig).

Bottom Line: A daily oral PLC treatment improved skin flap viability and associated with reactive oxygen species (ROS) reduction, inducible nitric oxide synthase (iNOS) and NO up-regulation, accelerated wound healing and increased capillary density, likely favoring dermal angiogenesis by up-regulation for iNOS, vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and reduction of NADPH-oxidase 4 (Nox4) expression.Interestingly, inhibition of β-oxidation counteracted the beneficial effects of PLC on oxidative stress and endothelial dysfunction.The beneficial effects of PLC likely derived from improvement of mitochondrial β-oxidation and reduction of Nox4-mediated oxidative stress and endothelial dysfunction.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedicine and Prevention, Anatomic Pathology, University of Tor Vergata, Rome, Italy.

ABSTRACT

Background: Impaired wound healing represents a high cost for health care systems. Endothelial dysfunction characterizes dermal microangiopathy and contributes to delayed wound healing and chronic ulcers. Endothelial dysfunction impairs cutaneous microvascular blood flow by inducing an imbalance between vasorelaxation and vasoconstriction as a consequence of reduced nitric oxide (NO) production and the increase of oxidative stress and inflammation. Propionyl-L-carnitine (PLC) is a natural derivative of carnitine that has been reported to ameliorate post-ischemic blood flow recovery.

Methods and results: We investigated the effects of PLC in rat skin flap and cutaneous wound healing. A daily oral PLC treatment improved skin flap viability and associated with reactive oxygen species (ROS) reduction, inducible nitric oxide synthase (iNOS) and NO up-regulation, accelerated wound healing and increased capillary density, likely favoring dermal angiogenesis by up-regulation for iNOS, vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and reduction of NADPH-oxidase 4 (Nox4) expression. In serum-deprived human dermal microvascular endothelial cell cultures, PLC ameliorated endothelial dysfunction by increasing iNOS, PlGF, VEGF receptors 1 and 2 expression and NO level. In addition, PLC counteracted serum deprivation-induced impairment of mitochondrial β-oxidation, Nox4 and cellular adhesion molecule (CAM) expression, ROS generation and leukocyte adhesion. Moreover, dermal microvascular endothelial cell dysfunction was prevented by Nox4 inhibition. Interestingly, inhibition of β-oxidation counteracted the beneficial effects of PLC on oxidative stress and endothelial dysfunction.

Conclusion: PLC treatment improved rat skin flap viability, accelerated wound healing and dermal angiogenesis. The beneficial effects of PLC likely derived from improvement of mitochondrial β-oxidation and reduction of Nox4-mediated oxidative stress and endothelial dysfunction. Antioxidant therapy and pharmacological targeting of endothelial dysfunction may represent a promising tool for the treatment of delayed wound healing or chronic ulcers.

No MeSH data available.


Related in: MedlinePlus