Clinical pulmonary autograft valves: pathologic evidence of adaptive remodeling in the aortic site.
ABSTRACT We studied the pathologic features, cellular phenotypes, and matrix remodeling of clinical pulmonary-to-aortic valve transplants functioning up to 6 years.
Nine autografts and associated vascular walls early (2-10 weeks) and late (3-6 years) postoperatively were examined by using routine morphologic methods and immunohistochemistry. In 4 cases autograft and homograft cusps were obtained from the same patients.
Autografts had near-normal trilaminar cuspal structure and collagen architecture and viable valvular interstitial and endothelial cells throughout the time course. In contrast, cusps of homografts used to replace the pulmonary valves in the same patients were devitalized. In early autograft explants, 19.3% +/- 2.4% of cuspal interstitial cells were myofibroblasts expressing alpha-actin. In contrast, myofibroblasts comprised only 6.0% +/- 1.1% of cells in late explants and 2.5% +/- 0.4% and 4.6% +/- 0.8% of cells in normal pulmonary and aortic valves, respectively (P <.05). In early autografts only 12.0% +/- 4.6% of endothelial cells expressed the systemic arterial endothelial cell marker EphrinB2, whereas later explants had 85.6% +/- 5.4% of endothelial cells expressing EphrinB2 (P <.05). In early autografts 43.8% +/- 8.8% of interstitial cells expressed metalloproteinase 13, whereas late autografts had 11.4% +/- 2.7% of interstitial cells expressing matrix metalloproteinase 13 (P <.05). Collagen content in autografts was comparable with that of normal valves and was higher than that seen in homograft valves (P <.005). However, autograft walls were damaged, with granulation tissue (early) and scarring, with focal loss of normal smooth muscle cells, elastin, and collagen (late).
The structure of pulmonary valves transplanted to the systemic circulation evolved toward that of normal aortic valves. Key processes in this remodeling included onset of a systemic endothelial cell phenotype and reversible plasticity of fibroblast-like valvular interstitial cells to myofibroblasts.
Article: Operación de RossRevista Argentina de Cardiología. 01/2010;
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ABSTRACT: Cardiovascular calcification is an independent risk factor for cardiovascular morbidity and mortality. This disease of dysregulated metabolism is no longer viewed as a passive degenerative disease, but instead as an active process triggered by pro-inflammatory cues. Furthermore, a positive feedback loop of calcification and inflammation is hypothesized to drive disease progression in arterial calcification. Both calcific aortic valve disease and atherosclerotic arterial calcification may possess similar underlying mechanisms. Early histopathological studies first highlighted the contribution of inflammation to cardiovascular calcification by demonstrating the accumulation of macrophages and T lymphocytes in `early' lesions within the aortic valves and arteries. A series of in vitro work followed, which gave a mechanistic insight into the stimulation of smooth muscle cells to undergo osteogenic differentiation and mineralization. The emergence of novel technology, in the form of animal models and more recently molecular imaging, has enabled accelerated progression of this field, by providing strong evidence regarding the concept of this disorder as an inflammatory disease. Although there are still gaps in our knowledge of the mechanisms behind this disorder, this review discusses the various studies that have helped form the concept of the inflammation-dependent cardiovascular calcification paradigm.Circulation Journal 05/2011; 75(6):1305-13. · 3.77 Impact Factor
Article: Molecular imaging insights into early inflammatory stages of arterial and aortic valve calcification.[show abstract] [hide abstract]
ABSTRACT: Traditional imaging modalities such as computed tomography, although perfectly adept at identifying and quantifying advanced calcification, cannot detect the early stages of this disorder and offer limited insight into the mechanisms of mineral dysregulation. This review presents optical molecular imaging as a promising tool that simultaneously detects pathobiological processes associated with inflammation and early stages of calcification in vivo at the (sub)cellular levels. Research into treatment of cardiovascular calcification is lacking, as shown by clinical trials that have failed to demonstrate the reduction of calcific aortic stenosis. Hence, the need to elucidate the pathways that contribute to cardiovascular calcification and to develop new therapeutic strategies to prevent or reverse calcification has driven investigations into the use of molecular imaging. This review discusses studies that have used molecular imaging methods to advance knowledge of cardiovascular calcification, focusing in particular on the inflammation-dependent mechanisms of arterial and aortic valve calcification.Circulation Research 05/2011; 108(11):1381-91. · 9.49 Impact Factor