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Bone marrow microvascular and neuropathic alterations in patients with critical limb ischemia
Martin Teraa1, Joost O Fledderus, Ramil I Rozbeh
1From 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.
Insights
Critical limb ischemia (CLI) significantly impacts bone marrow (BM), reducing microvascular density and altering nerve function. These changes occur regardless of diabetes status in patients with CLI.
Area of Science:
- Vascular biology
- Neurology
- Hematology
Background:
- The bone marrow's role in critical limb ischemia (CLI) is understudied.
- Understanding bone marrow (BM) changes in CLI is crucial for developing new therapies.
Purpose of the Study:
- To investigate microvascular and neuropathic alterations in the bone marrow (BM) of patients with CLI.
- To determine if diabetes mellitus affects these BM changes in CLI patients.
Main Methods:
- Bone marrow (BM) biopsies were collected from 33 CLI patients and 12 controls.
- Immunohistochemistry and histomorphometry were used to assess microvascular density and neuronal innervation (pan-neuronal and sympathetic).
Main Results:
- CLI patients exhibited significantly reduced microvascular density in BM compared to controls.
- Both sympathetic and pan-neuronal innervation were significantly decreased in the BM of CLI patients.
- No significant differences in microvascular density or innervation were found between CLI patients with and without diabetes mellitus.
Conclusions:
- Critical limb ischemia (CLI) is associated with detrimental microvascular and neuropathic changes in the bone marrow (BM).
- These bone marrow (BM) changes in CLI patients are independent of diabetes mellitus status.
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.
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