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Akap1 Regulates Vascular Function and Endothelial Cells Behavior.
Journal article

Akap1 Regulates Vascular Function and Endothelial Cells Behavior.

  • Schiattarella GG From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.).
  • Cattaneo F From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.).
  • Carrizzo A From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.).
  • Paolillo R From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.).
  • Boccella N From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.).
  • Ambrosio M From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.).
  • Damato A From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.).
  • Pironti G From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.).
  • Franzone A From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.).
  • Russo G From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.).
  • Magliulo F From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.).
  • Pirozzi M From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.).
  • Storto M From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.).
  • Madonna M From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.).
  • Gargiulo G From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.).
  • Trimarco V From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.).
  • Rinaldi L From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.).
  • De Lucia M From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.).
  • Garbi C From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.).
  • Feliciello A From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.).
  • Esposito G From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.).
  • Vecchione C From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.).
  • Perrino C From the Department of Advanced Biomedical Sciences (G.G.S., F.C., R.P., N.B., A.F., F.M., G.G., G.E., C.P.), Department of Molecular Medicine and Medical Biotechnologies (G.R., L.R., C.G., A.F.), and Department of Neuroscience, Reproductive Science and Odontostomatology (V.T.), University of Naples "Federico II", Italy; IRCCS Neuromed, Pozzilli, Italy (A.C., M.A., A.D., M.S., M.M., M.D.L., C.V.); Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (G.P.); Department of Cardiology, Bern University Hospital, University of Bern, Switzerland (A.F., G.G.); Institute of Protein Biochemistry, Italian National Research Council, Naples (M.P.); and Department of Medicine and Surgery, University of Salerno, Baronissi, Italy (C.V.). perrino@unina.it cvecchione@unisa.it.
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  • 2018-01-17
Published in:
  • Hypertension (Dallas, Tex. : 1979). - 2018
angiogenesis
hypertension
ischemia
mitochondria
reactive oxygen species
A Kinase Anchor Proteins
Analysis of Variance
Animals
Cell Movement
Cells, Cultured
Disease Models, Animal
Endothelial Cells
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitochondria
Neovascularization, Pathologic
Nitric Oxide
Phosphorylation
Random Allocation
Reactive Oxygen Species
Reference Values
Risk Factors
Statistics, Nonparametric
Vascular Diseases
English MitoAKAPs (mitochondrial A kinase anchoring proteins), encoded by the Akap1 gene, regulate multiple cellular processes governing mitochondrial homeostasis and cell viability. Although mitochondrial alterations have been associated to endothelial dysfunction, the role of mitoAKAPs in the vasculature is currently unknown. To test this, postischemic neovascularization, vascular function, and arterial blood pressure were analyzed in Akap1 knockout mice (Akap1-/- ) and their wild-type (wt) littermates. Primary cultures of aortic endothelial cells (ECs) were also obtained from Akap1-/- and wt mice, and ECs migration, proliferation, survival, and capillary-like network formation were analyzed under different experimental conditions. After femoral artery ligation, Akap1-/- mice displayed impaired blood flow and functional recovery, reduced skeletal muscle capillary density, and Akt phosphorylation compared with wt mice. In Akap1-/- ECs, a significant enhancement of hypoxia-induced mitophagy, mitochondrial dysfunction, reactive oxygen species production, and apoptosis were observed. Consistently, capillary-like network formation, migration, proliferation, and AKT phosphorylation were reduced in Akap1-/- ECs. Alterations in Akap1-/- ECs behavior were also confirmed in Akap1-/- mice, which exhibited a selective reduction in acetylcholine-induced vasorelaxation in mesenteric arteries and a mild but significant increase in arterial blood pressure levels compared with wt. Finally, overexpression of a constitutively active Akt mutant restored vascular reactivity and ECs function in Akap1-/- conditions. These results demonstrate the important role of mitoAKAPs in the modulation of multiple ECs functions in vivo and in vitro, suggesting that mitochondria-dependent regulation of ECs might represent a novel therapeutic approach in cardiovascular diseases characterized by endothelial dysfunction.
Language
  • English
Open access status
closed
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https://sonar.ch/global/documents/185089
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