Bone Marrow Microvascular and Neuropathic Alterations in Critical Limb Ischemia Patients
Rationale: The impact of severe cardiovascular disease and critical limb ischemia (CLI) on the bone marrow (BM) is largely unknown.
Objective: Investigate microvascular and neuropathic changes in BM of CLI patients.
Methods and Results: BM biopsies were obtained from CLI patients (n=33) included in the Juventas-trial (NCT00371371) and controls (n=12). We performed immunohistochemistry and histomorphometry of the BM to assess microvascular density (MVD), and to evaluate pan-neuronal and sympathetic innervation, which is involved in progenitor cell (PC) mobilization. MVD was significantly reduced in CLI compared to controls (P=0.01), as was sympathetic (P=0.047) and pan-neuronal innervation (P=0.006). No differences in MVD and sympathetic or pan-neuronal innervation were observed between CLI patients with and without diabetes.
Conclusions: CLI is associated with BM microvascular and neuropathic changes, both in patients with and without diabetes.
- critical limb ischemia
- bone marrow
- peripheral artery disease
- peripheral vascular disease
- vascular biology
- structural biology
- Received October 6, 2013.
- Revision received November 8, 2013.
- Accepted November 11, 2013.