Bone marrow microvascular and neuropathic alterations in patients with critical limb ischemia.
BACKGROUND
The impact of severe cardiovascular disease and critical limb ischemia (CLI) on the bone marrow (BM) is largely unknown.


OBJECTIVE
To investigate microvascular and neuropathic changes in BM of patients with CLI.


RESULTS
BM biopsies were obtained from patients with CLI (n=33) included in the Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-arterial Supplementation (JUVENTAS) trial (NCT00371371) and controls (n=12). We performed immunohistochemistry and histomorphometry of the BM to assess microvascular density and to evaluate pan-neuronal and sympathetic innervation, which is involved in progenitor cell mobilization. Microvascular density was reduced significantly in CLI compared with controls (P=0.01), as was sympathetic (P=0.047) and pan-neuronal innervation (P=0.006). No differences in microvascular density and sympathetic or pan-neuronal innervation were observed between patients with CLI with and without diabetes mellitus.


CONCLUSIONS
CLI is associated with BM microvascular and neuropathic changes, both in patients with and without diabetes mellitus.
From the Department of Nephrology and Hypertension (M.T., J.O.F., R.I.R., M.C.V.), Department of Vascular Surgery (M.T.), and Department of Pathology (R.J.L.), University Medical Center Utrecht, Utrecht, The Netherlands.
Martin
M
Teraa
Joost O
JO
Fledderus
Ramil I
RI
Rozbeh
Roos J
RJ
Leguit
Marianne C
MC
Verhaar
D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D001853:Bone Marrow / Q000098:blood supply* / Q000294:innervation*; D001856:Bone Marrow Examination; D016022:Case-Control Studies; D016638:Critical Illness; D003920:Diabetes Mellitus / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007511:Ischemia / Q000473:pathology*; D008297:Male; D055806:Microvessels / Q000737:chemistry / Q000473:pathology*; D008875:Middle Aged; D013564:Sympathetic Nervous System / Q000737:chemistry / Q000473:pathology*
D015415:Biomarkers
bone marrow; diabetic neuropathies; microvasculature; peripheral arterial disease