Therapeutic effects of autologous bone marrow cells and metabolic intervention in the ischemic hindlimb of spontaneously hypertensive rats involve reduced cell senescence and CXCR4/Akt/eNOS Pathways

Filomena De Nigris, Maria Luisa Balestrieri, Sharon Williams-Ignarro, Francesco P. D'Armiento, Lilach O Lerman, Russell Byrns, Ettore Crimi, Antonio Palagiano, Gennaro Fatigati, Louis J. Ignarro, Claudio Napoli

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Peripheral arterial disease (PAD) is a major health problem, especially when associated with severe hypertension. Administration of autologous bone marrow cells (BMCs) is emerging as a novel intervention to induce neoangiogenesis in ischemic limb models and in patients with PAD. This study evaluates the neovascularization capacity of BMCs alone or in combination with metabolic cotreatment (0.8% vitamin E, 0.05% vitamin C, and 5% of L-arginine) in a rat model of ischemic hindlimbs of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Molecular mechanisms were investigated in bone marrow-derived endothelial progenitor cells (BM-EPC) derived from rats. BMC therapy increased blood flow and capillary densities and Ki67 proliferative marker, and it decreased interstitial fibrosis. These effects were amplified by metabolic cotreatment, an intervention that induces vascular protection at least partly through the nitric oxide (NO)/endothelial nitric oxide synthase (eNOS) pathway, reduction of systemic oxidative stress, and macrophage activation. In addition, BMC therapy alone and, more consistently, in combination with metabolic treatment, ameliorated BM-EPC functional activity via decreased cellular senescence and improved homing capacity by increasing CXCR4-expression levels. These data suggest potential therapeutic effects of autologous BMCs and metabolic treatment in hypertensive PAD patients.

Original languageEnglish (US)
Pages (from-to)424-433
Number of pages10
JournalJournal of Cardiovascular Pharmacology
Volume50
Issue number4
DOIs
StatePublished - Oct 2007

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Nitric Oxide Synthase Type III
Cell Aging
Therapeutic Uses
Inbred SHR Rats
Hindlimb
Bone Marrow Cells
Peripheral Arterial Disease
Cell- and Tissue-Based Therapy
Bone Marrow
Inbred WKY Rats
Macrophage Activation
Vitamin E
Ascorbic Acid
Blood Vessels
Arginine
Nitric Oxide
Oxidative Stress
Fibrosis
Extremities
Hypertension

Keywords

  • Bone marrow cell
  • Hypertension
  • Ischemic hindlimb
  • L-arginine
  • Nitric oxide
  • Peripheral arterial disease

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Therapeutic effects of autologous bone marrow cells and metabolic intervention in the ischemic hindlimb of spontaneously hypertensive rats involve reduced cell senescence and CXCR4/Akt/eNOS Pathways. / Nigris, Filomena De; Balestrieri, Maria Luisa; Williams-Ignarro, Sharon; D'Armiento, Francesco P.; Lerman, Lilach O; Byrns, Russell; Crimi, Ettore; Palagiano, Antonio; Fatigati, Gennaro; Ignarro, Louis J.; Napoli, Claudio.

In: Journal of Cardiovascular Pharmacology, Vol. 50, No. 4, 10.2007, p. 424-433.

Research output: Contribution to journalArticle

Nigris, Filomena De ; Balestrieri, Maria Luisa ; Williams-Ignarro, Sharon ; D'Armiento, Francesco P. ; Lerman, Lilach O ; Byrns, Russell ; Crimi, Ettore ; Palagiano, Antonio ; Fatigati, Gennaro ; Ignarro, Louis J. ; Napoli, Claudio. / Therapeutic effects of autologous bone marrow cells and metabolic intervention in the ischemic hindlimb of spontaneously hypertensive rats involve reduced cell senescence and CXCR4/Akt/eNOS Pathways. In: Journal of Cardiovascular Pharmacology. 2007 ; Vol. 50, No. 4. pp. 424-433.
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