Pleiotrophin promotes capillary-like sprouting from senescent aortic rings

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Abstract

Highlights

★ We examine pleiotrophin (PTN) effect on capillary sprouting during aging. ★ Capillary sprouting is lower in senescent aortic rings as compared to adults. ★ Capillary formation is improved after PTN treatment in explanted vessels at all ages. ★ Angiogenic effects of PTN and VEGF are of the same extent in senescent vessels. ★ PTN could be a promising therapeutic agent for revascularization therapy during aging.

Background

Pleiotrophin (PTN) is a heparin-binding growth factor involved in angiogenesis during development and tumor growth. Plasmid therapy with PTN also induces angiogenesis after myocardial infarction. During aging, angiogenesis is impaired and we therefore examined whether a growth factor therapy with PTN is able to restore neovascularization.

Methods

We evaluated the PTN effects on capillary-like endothelial sprouting in adult (n = 10) and senescent (n = 10) rats, using an ex vivo model of explanted aortic segments in culture. Freshly cut thoracic aortic rings from 3 and 24 month old (mo) rats (both n = 12) were cultured in a 3-dimensional collagen matrix with or without addition of recombinant human PTN (2.5–250 ng/ml) or Vascular Endothelial Growth Factor-165 (VEGF) (1–100 ng/ml) and the length of developed capillary network was quantified at day 3 and 6 by image analysis.

Results

After 6 days of culture, capillary-like tube formation was lower in control conditions in 24 mo aortic rings than in 3 mo rings. Addition of PTN increased dose-dependently the length of capillary-like tube formation in both 3 and 24 mo rings (P < 0.001 and P < 0.001 respectively). Age-associated impairment of capillary-like tube formation had been successfully restored in senescent aortic segments by PTN treatment. PTN induced development of capillary network similar to that observed with VEGF therapy with doses equal or superior to 10 ng/ml.

Conclusion

PTN is able to induce ex vivo angiogenesis during aging and might be a new promising therapy to induce neovascularization in aged tissues as well as after age-associated cardiac, hindlimb or cerebral ischemia.

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