Bone marrow microvascular and neuropathic alterations in patients with critical limb ischemia

RATIONALE: 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.

METHODS AND 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.