Cited 8 times since 2012 (0.7 per year) source: EuropePMC Histology and histopathology, Volume 27, Issue 3, 1 1 2012, Pages 387-396 Visualizing TGF-β and BMP signaling in human atherosclerosis: a histological evaluation based on Smad activation. van Dijk RA, Engels CC, Schaapherder AF, Mulder-Stapel A, Ten Dijke P, Hamming JF, Lindeman JH
Background
The TGF-β superfamily members transforming growth factor-β (TGF-β/Activin) and bone morphogenetic proteins (BMP) have been implicated in the pathogenesis of atherosclerosis. However, their role in human disease remains controversial. In this study we used Smad phosphorylation as a read out for TGF-β and BMP signaling during the initiation, progression and (de)stabilization of human atherosclerotic disease.
Material and methods
A systematic analysis was performed in 114 peri-renal aortic patches (stained with Movat Pentachrome, H&E, pSmad2, pSmad1,5,8 and PAI-1) covering the entire atherosclerotic spectrum (van Dijk, 2010). Immunostaining against T-cells (CD3) and monocytes and macrophages (CD68) was used to explore a putative association between TGF-β and BMP signaling and vascular inflammation.
Results
Smad phosphorylation was present within the normal arterial wall in approximately 10% of the endothelial cells and intimal smooth muscle cells. A significant increase in pSmad2 and pSmad1,5,8 positivity was found in non-progressive lesions (>50% positivity). No further increase or decrease was found in the progressive atherosclerotic lesions, vulnerable and stabilized lesions. No association was found between TGF-β and BMP signaling and CD3 and CD68 expression, nor cap thickness.
Conclusion
Activation of the TGF-β and BMP pathways is an early event in atherosclerotic lesion formation. No significant relationships were found between Smad phosphorylation and vessel wall inflammation or plaque vulnerability.
