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Recovery of limb perfusion and function after hindlimb ischemia is impaired by arterial calcification
Sara L Zettervall1, Xue-Lin Wang1, Stephanie Monk1
1Division of Vascular and Endovascular Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Insights
Medial artery calcification impairs blood flow recovery after limb ischemia in rats. This vascular condition, common in peripheral artery disease (PAD), worsens outcomes and highlights the need to manage arterial calcification.
Area of Science:
- Vascular Biology and Medicine
- Cardiovascular Research
- Regenerative Medicine
Background:
- Medial artery calcification involves calcium hydroxyapatite deposition and osteogenic changes in vascular smooth muscle cells.
- It is prevalent in chronic kidney disease, diabetes, and peripheral artery disease (PAD), correlating with higher amputation rates in lower extremities.
- The impact of medial calcification on tissue perfusion and functional recovery following acute limb ischemia is not fully understood.
Purpose of the Study:
- To investigate the effects of medial artery calcification on hindlimb perfusion and functional recovery after induced ischemia in a rat model.
- To elucidate the role of medial calcification in the pathophysiology of acute limb ischemia.
Main Methods:
- Medial artery calcification was induced using vitamin D3 (VitD3) injection in rats.
- Acute limb ischemia was simulated via femoral artery ligation.
- Laser Doppler perfusion imaging, histological analysis, and hemodynamic assessments were employed to evaluate outcomes.
Main Results:
- VitD3-induced medial calcification significantly impaired perfusion recovery post-ischemia compared to controls.
- Rats with medial calcification exhibited worse ischemia scores and delayed functional recovery.
- Increased arterial stiffness was observed in VitD3-injected rats, while cardiac function remained preserved.
Conclusions:
- Medial artery calcification contributes to impaired perfusion recovery in acute limb ischemia, potentially by altering vascular compliance.
- Despite preserved capillary density and muscle morphology, functional deficits were evident.
- Slowing or reducing arterial calcification may improve clinical outcomes for patients with PAD.
Abstract:
Medial artery calcification results from deposition of calcium hydroxyapatite crystals on elastin layers, and osteogenic changes in vascular smooth muscle cells. It is highly prevalent in patients with chronic kidney disease, diabetes, and peripheral artery disease (PAD), and when identified in lower extremity vessels, it is associated with increased amputation rates. This study aims to evaluate the effects of medial calcification on perfusion and functional recovery after hindlimb ischemia in rats. Medial artery calcification and acute limb ischemia were induced by vitamin D3 (VitD3 ) injection and femoral artery ligation in rats. VitD3 injection robustly induced calcification in the medial layer of femoral arteries in vivo. Laser Doppler perfusion imaging revealed that perfusion decreased and then partially recovered after hindlimb ischemia in vehicle-injected rats. In contrast, VitD3 -injected rats showed markedly impaired recovery of perfusion following limb ischemia. Accordingly, rats with medial calcification showed worse ischemia scores and delayed functional recovery compared with controls. Immunohistochemical and histological staining did not show differences in capillary density or muscle morphology between VitD3 - and vehicle-injected rats at 28 days after femoral artery ligation. The evaluation of cardiac and hemodynamic parameters showed that arterial stiffness was increased while cardiac function was preserved in VitD3 -injected rats. These findings suggest that medial calcification may contribute to impaired perfusion in PAD by altering vascular compliance, however, the specific mechanisms remain poorly understood. Reducing or slowing the progression of arterial calcification in patients with PAD may improve clinical outcomes.
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