Hypoxic preconditioning increases survival and angiogenic potency of peripheral blood mononuclear cells via oxidative stress resistance.

Abstract

Cell-based angiogenesis is a promising treatment for ischemic diseases; however, the survival of implanted cells is impaired by oxidative stress in the ischemic microenvironment. We tested the hypothesis that hypoxic preconditioning of implanted cells enhances their resistance against oxidative stress, increasing cell survival and angiogenic potency after implantation into ischemic tissue. Mouse peripheral blood mononuclear cells (PBMNCs) were collected and subjected to hypoxic preconditioning by culture for 24 h in 2% O(2) at 33 degrees C. Hypoxic preconditioning of PBMNCs increased the expression of various genes related to antioxidant and survival signals remarkably. Compared with cells cultured under normoxia, the hypoxia-preconditioned PBMNCs showed significantly lower reactive oxygen species (ROS) accumulation and higher cell survival under oxidative stress induced by LY-83583 (a superoxide generator). Three days after intramuscular implantation into the ischemic hindlimbs of mice, survival of the hypoxia-preconditioned PBMNCs was high, whereas that of the normoxia-cultured PBMNCs was relatively low. Furthermore, 28 days after treatment microvessel density and blood flow in the ischemic hindlimbs were significantly better in the mice implanted with hypoxia-preconditioned PBMNCs than in those implanted with normoxia-cultured PBMNCs. Hypoxic preconditioning increased the survival and angiogenic potency of PBMNCs, through oxidative stress resistance mechanisms.

• Authors: Masayuki Kubo, Tao-Sheng Li, Ryo Suzuki, Bungo Shirasawa, Noriyasu Morikage, Mako Ohshima, Shu-Lan Qin, Kimikazu Hamano
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 294 Issue 2 Pg. H590-5 (Feb 2008) ISSN: 0363-6135 [Print] United States
• PMID: 18156196 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aminoquinolines
• Enzyme Inhibitors
• Reactive Oxygen Species
• RNA
• 6-anilino-5,8-quinolinedione
• Guanylate Cyclase

Topics

• Aminoquinolines (pharmacology)
• Animals
• Capillaries (physiology)
• Cell Survival (physiology)
• Enzyme Inhibitors (pharmacology)
• Gene Expression (physiology)
• Guanylate Cyclase (antagonists & inhibitors)
• Hindlimb (blood supply)
• Hypoxia (physiopathology)
• Ischemic Preconditioning, Myocardial
• Mice
• Monocytes (metabolism, physiology)
• Neovascularization, Physiologic (physiology)
• Oxidative Stress (physiology)
• RNA (biosynthesis, genetics)
• Reactive Oxygen Species (metabolism)
• Regional Blood Flow (physiology)
• Reverse Transcriptase Polymerase Chain Reaction