Autor:innen:
Larissa Schawe | 1Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health | Germany
Dr. med. Raphael Donatus Hein | 1Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health | Germany
Dr. med. Jan Paul Bernhard Frese | 1Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health | Germany
Ben Raude | 1Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health | Germany
Jan Christoph Carstens | 1Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health | Germany
Dr. Safwan Omran | 1Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health | Germany
Dr. Nina Hering | 1Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health | Germany
Prof. Dr. med. Andreas Greiner | 1Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health | Germany
Prof. Dr. Irene Hinterseher | 1Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health | Germany
Background Studies on pro-angiogenic growth factors as a treatment for peripheral artery disease (PAD) seem promising but have not yet delivered satisfactory results in the clinics. Recent research highlighted higher levels of vascular endothelial growth factor (VEGF) in serum as well as locally - in muscle biopsies - of PAD patients compared to controls. After exercise training, the local VEGF levels are reduced significantly.
Objective In the present study, we measured VEGF levels in muscle biopsies obtained before and after surgical revascularization. We hypothesized that VEGF is increased in ischemic muscles in comparison to non-ischemic muscle biopsies of the same patient. We further envisaged that, after bypass surgery, levels in the revascularized muscle would decrease from preoperative levels.
Material and Methods The study cohort consisted of ten PAD patients (8 male, ages 68.6y ± 5.74y) with superficial femoral artery (SFA) stenosis. Revascularization of the SFA was performed by endarterectomy +/- percutaneous transluminal angioplasty (PTA) or bypass surgery. Muscle biopsies of the gastrocnemius and vastus muscle were obtained during surgery as well as 8 weeks postoperatively. Biopsies of the gastrocnemius muscle are regarded as ischemic muscle biopsies and the vastus biopsies as controls. VEGF levels in skeletal muscle lysates were determined by ELISA technique.
Results Preoperative VEGF levels were 74.40 pg/mL (IQR 23.60) in gastrocnemius, and 54.52 pg/mL (IQR 24.65) in vastus muscle biopsies. Postoperative values decreased significantly (P < 0.01) to 49.37 pg/mL (IQR 31.79) in gastrocnemius biopsies. No significant reduction was seen in vastus muscle biopsies with postoperative VEGF values of 50.43 pg/mL (IQR 37.10) (P=0.33). Median preoperative VEGF levels were 1.4 times higher in gastrocnemius muscle biopsies compared to vastus muscles biopsies (p=0.07).
Discussion and conclusion The present study supports previous findings in which VEGF levels are elevated in PAD. Since all patients enrolled in this study had indications for revascularization, it can be concluded that VEGF levels were insufficient to form collaterals or that the downstream response to elevated VEGF was impaired in PAD muscles. Recent studies have already shown an insufficient response to growth factors in diabetic patients, which includes 30% of the study population.
Serum VEGF is increased in various types of cancer with values ranging from 200 to 700 pg/mL5. Here, the highest VEGF concentration was 123 pg/mL with average levels below 100 pg/mL. This could contribute to the hypothesis of inadequate VEGF levels for a sufficient angiogenesis. Further studies would be necessary to understand angiogenesis in PAD patients, in order to improve and target treatment with pro-angiogenic factors, if this strategy remains.