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Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Vascular remodeling and media calcification increases arterial stiffness in chronic kidney disease
Alexandra Gauthier-Bastien1, Roth-Visal Ung, Richard Larivière
1Nephrology & Hypertension Research Unit, CHU de Québec Research Centre, L'Hôtel-Dieu de Québec Hospital and Department of Medicine, Université Laval , Quebec , Canada.
Insights
Chronic kidney disease (CKD) in rats leads to arterial stiffness. Smooth muscle cell changes and blood vessel remodeling contribute to this stiffness and vascular calcification in CKD.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Vascular Biology
Background:
- Cardiovascular disease is a leading cause of mortality in chronic kidney disease (CKD) patients.
- Arterial stiffness and vascular calcification are key non-traditional risk factors for cardiovascular disease in CKD.
- The study investigates the role of smooth muscle cell differentiation and vascular remodeling in arterial stiffness within CKD.
Purpose of the Study:
- To investigate the mechanisms linking smooth muscle cell differentiation to osteoblast-like cells.
- To understand the role of vascular media remodeling and calcification in arterial stiffness in CKD.
- To analyze the changes in cellular components of the blood vessel wall associated with increased arterial stiffness.
Main Methods:
- CKD and vascular calcification induced in rats via subtotal nephrectomy, high calcium/phosphate diet, and vitamin D.
- Hemodynamic parameters and pulse wave velocity (PWV) measured at weeks 3-6.
- Vascular media calcification and remodeling assessed using von Kossa staining and immunofluorescence for osteocalcin, elastin, α-SMA, and collagen-1.
Main Results:
- CKD rats showed significantly increased pulse pressure and PWV, with marked media calcification.
- Osteocalcin expression increased, while α-smooth muscle actin (α-SMA) and elastin levels decreased in calcified areas.
- Reduced α-SMA and elastin levels correlated inversely with PWV, indicating increased arterial stiffness.
Conclusions:
- Smooth muscle cell differentiation into osteoblast-like cells contributes to arterial stiffness in CKD.
- Vascular media remodeling, including elastic lamella disruption and collagen deposition, is associated with increased arterial stiffness.
- These cellular and structural changes are key factors in the development of arterial stiffness in CKD with vascular calcification.
Background:
Cardiovascular disease is the most common cause of death in patients with chronic kidney disease (CKD). Arterial stiffness and calcification are non-traditional risk factors of cardiovascular disease in CKD. In CKD rats, we investigated the involvement of smooth muscle cells differentiation to osteoblast-like cells and blood vessel wall remodeling, associated with media calcification, in arterial stiffness.
Method:
CKD with vascular calcification was induced by subtotal nephrectomy followed by treatment with a high calcium and phosphate diet, and vitamin D supplementation (Ca/P/VitD). At week 3-6, hemodynamic parameters and pulse wave velocity (PWV) were assessed. Vascular media calcification and remodeling were determined by histological von Kossa staining and confocal immunofluorescence analysis of osteocalcin, elastin, α-smooth muscle actin (α-SMA) and collagen-1.
Results:
Treatment of CKD rats with Ca/P/VitD, but not normal animals, induced a significant increase in pulse pressure and PWV (p < 0.05) and marked calcification in the media. In calcification areas, de novo expression of osteocalcin was observed, whereas α-SMA immunofluorescence levels were reduced (p < 0.01). The immunofluorescence levels of elastin were also reduced, which was related to disruption of elastic lamella. In contrast, collagen-1 immunofluorescence levels in areas of calcification were increased (p < 0.01). Changes in both α-SMA and elastin inversely correlated with the PWV.
Conclusion:
This study indicate that smooth muscle cells differentiation to osteoblast-like cells and the associated media remodeling, which includes disruption of elastic lamellas and deposition of collagen are, at least in part, associated with the increased arterial stiffness observed in CKD rats with vascular calcification.
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