Platelet-derived growth factor B retention is essential for development of normal structure and function of conduit vessels and capillaries

• 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.

Nyckelord

Animals

Aorta

Thoracic/pathology/*physiopathology

Blood Pressure

Capillaries/pathology/physiopathology

Cardiomegaly/diagnosis/genetics

Endothelium

Vascular/pathology/physiopathology

Male

Mice

Mice

Knockout

Motor Activity

Muscle

Skeletal/*blood supply

Myography

Oxygen Consumption

Proto-Oncogene Proteins c-sis/deficiency/genetics/*physiology

Renin/blood

Tunica Media/metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)