Simvastatin augments revascularization and reperfusion in a murine model of hind limb ischemia - Multimodal imaging assessment

Autor: R. Boominathan, Nalini Shenoy, Michael Ng, Peter Cheng, Julian L. Goggi, Sakthivel Sekar, Kishore Bhakoo
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Vascular Endothelial Growth Factor A
Cancer Research
medicine.medical_specialty
Simvastatin
medicine.medical_treatment
Ischemia
Neovascularization
Physiologic
Hindlimb
030204 cardiovascular system & hematology
Revascularization
Multimodal Imaging
03 medical and health sciences
Mice
0302 clinical medicine
Internal medicine
Spect imaging
medicine
Animals
Radiology
Nuclear Medicine and imaging
cardiovascular diseases
Tomography
Emission-Computed
Single-Photon
Mice
Inbred BALB C
medicine.diagnostic_test
business.industry
Muscles
Technetium
Magnetic resonance imaging
medicine.disease
Magnetic Resonance Imaging
Surgery
Capillaries
Disease Models
Animal
030104 developmental biology
Amputation
Gene Expression Regulation
Regional Blood Flow
Cardiology
Molecular Medicine
business
Perfusion
Oligopeptides
medicine.drug
Zdroj: Nuclear medicine and biology. 46
ISSN: 1872-9614
Popis: Introduction Peripheral artery disease can lead to severe disability and limb loss. Therapeutic strategies focussing on macrovascular repair have shown benefit but have not significantly reduced amputation rates in progressive PAD. Proangiogenic small molecule therapies may substantially improve vascularisation in limb ischemia. The purpose of the current study was to assess the proangiogenic effects of simvastatin in a murine model of hind limb ischemia using longitudinal multimodal imaging. Methods Mice underwent surgical intervention to induce hind limb ischemia, and were treated with simvastatin orally for 28days. Neovascularisation was assessed using 99m Tc-RGD SPECT imaging, and macrovascular volume was assessed by quantitative time of flight MRI. At each imaging time point, VEGF expression and capillary vessel density were quantified using immunohistochemical analysis. Results Simvastatin significantly increased 99m Tc-RGD retention in the ischemic hind limb by day 3 post-surgery, with maximal retention at day 8. Vascular volume was significantly increased in the ischemic hind limb of simvastatin treated animals, but only by day 22. Immunohistochemical analysis shows that simvastatin significantly augmented tissue VEGF expression from day 8 with increase in capillary density (CD31 + ) from day 14. Conclusions Early assessment of proangiogenic therapy efficacy can be identified using 99m Tc-RGD SPECT, which displays significant increases in retention before macrovascular volume changes are measureable with MRI. Advances in knowledge and implications for patient care Simvastatin offers an effective proangiogenic therapy as an adjunct for management of limb ischemia. Simvastatin induces integrin expression and vascular remodeling leading to neovascularisation and improved perfusion.
Databáze: OpenAIRE
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