Bone Marrow Microvascular and Neuropathic Alterations in Patients With Critical Limb Ischemia

Abstract

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.