Key result
PDGF-B retention motif deletion in mice resulted in increased aortic diameter and stiffness, endothelial dysfunction, and decreased skeletal muscle capillary density.
Extracellular retention of PDGF-B during development is essential for normal conduit vessel function, adequate capillary density, and oxygen delivery to skeletal muscle in mice.
Findings in mice should not change practice; leaves open PDGF-B retention as a therapeutic target in human vascular disease.
OBJECTIVE: Extracellular retention of PDGF-B has been proposed to play an important role in PDGF-B signalling. We used the PDGF-B retention motif knockout mouse (RetKO) to study the effects of retention motif deletion on development of micro- and macrovascular structure and function. METHODS: Passive and active properties of conduit vessels were studied using myograph techniques and histological examination. Capillary structure and function was studied using measurements of capillary density in skeletal muscle and by assessing aerobic physical performance in a treadmill setup. Cardiac function was assessed using echocardiography. RESULTS: Myograph experiments revealed an increased diameter and stiffness of the aorta in RetKO. Histological examination showed increased media collagen content and a decreased number of aortic wall layers, however with a similar number of vascular smooth muscle cells. This outward eutrophic remodelling of the aorta was accompanied by endothelial dysfunction. RetKO showed decreased capillary density in skeletal muscle and signs of a defective delivery of capillary oxygen to skeletal muscle, as shown by a decreased physical performance. In RetKO mice, echocardiography revealed an adaptive eccentric cardiac hypertrophy. CONCLUSION: We conclude that retention of PDGF-B during development is essential for a normal conduit vessel function in the adult mouse. Furthermore, PDGF-B retention is also necessary for the development of an adequate capillary density, and thereby for a normal oxygen delivery to skeletal muscle. The lack of primary effects on cardiac function supports the redundant role of PDGF-B in cardiac development.
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Nyström et al. (2006) studied this question. PDGF-B retention motif deletion (RetKO) vs. Wild-type was evaluated on Micro- and macrovascular structure and function. PDGF-B retention motif deletion in mice resulted in increased aortic diameter and stiffness, endothelial dysfunction, and decreased skeletal muscle capillary density.
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