VEGF and VEGF receptor expression in human chronic critical limb ischaemia.
OBJECTIVE
This study quantified endogenous VEGF and VEGF receptor expression in limbs of patients with chronic critical limb ischaemia (CLI).


METHODS
Skin and muscle biopsies were obtained from the legs of 25 patients undergoing limb amputation for CLI. Samples were obtained at the amputation level (thigh or calf) and, distally, from the foot and in the vicinity of ischaemic ulcers and gangrene. Control biopsies were obtained from patients undergoing amputation for non-arterial reasons or knee arthroplasty (n=7). VEGF protein levels in tissue lysates were measured by ELISA, and VEGF and KDR mRNA levels were determined using quantitative PCR.


RESULTS
At the amputation level, VEGF protein and VEGF and KDR mRNA levels in CLI limbs were similar to those in controls. In the foot VEGF mRNA in skin (P=0.005) and VEGF protein levels in muscle (P=0.02) were elevated compared to levels in a proximal biopsy from the same limb. VEGF and KDR mRNA levels in the vicinity of gangrene/ulcers (VEGF P=0.01, KDR P=0.03) also were elevated.


CONCLUSIONS
VEGF expression is not deficient in CLI. Indeed, it is elevated at distal sites in the ischaemic limb. These findings question the rationale for VEGF supplementation in CLI.
Choksy
S
S
Division of Clinical Sciences (North), University of Sheffield, Clinical Sciences Centre, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK. sohail.choksy@sheffield.ac.uk
Pockley
A G
AG
Wajeh
Y E
YE
Chan
P
P
D000368:Aged; D000369:Aged, 80 and over; D000671:Amputation, Surgical; D002908:Chronic Disease; D005260:Female; D015870:Gene Expression; D006801:Humans; D007511:Ischemia / Q000378:metabolism* / Q000601:surgery; D007866:Leg / Q000098:blood supply* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor