Copyright © 2006, European Society of Cardiology
Platelet-derived growth factor B retention is essential for development of normal structure and function of conduit vessels and capillaries
aInstitute of Physiology and Pharmacology, Department of Physiology, Göteborg University, Sweden
bVascular Biology Lab, London Research Institute, Cancer Research UK, UK
cVascular Biology Laboratory, Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Sweden
dRCEM and Wallenberg Laboratory, Sahlgrenska University Hospital, Sweden
eDepartment of Biomedical Chemistry, Göteborg University, Sweden
fIMB, Physiology and Pharmacology, SDU, Odense University, Denmark
gDepartment of Physiology, Monash University, Australia
hDepartment of Clinical Physiology, Cardiovascular Institute, Göteborg University, Sweden
* Corresponding author. Institute of Physiology and Pharmacology, Department of Physiology, Göteborg University, P.O. Box 432, Medicinaregatan 11, S405 30 Göteborg, Sweden. Email address: henrik.nystrom{at}fysiologi.gu.se
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.
KEYWORDS Platelet-derived growth factor B; Extracellular matrix; Vascular function; Cardiac function; In vivo physiology
Parts of this work have previously been published in abstract-form at the XIIIth International Symposium on Atherosclerosis, 2003, Kyoto, Japan.