الفهرس 
Pulmonary HypertensionOnly 14 pages are availabe for public view
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Abstract
Pulmonary hypertension (PH) is still a major and growing public health problem that has shown increasing morbidity and mortality during the last decades. Therefore, the prognostic evaluation and risk stratification of PH patients continues to increase in importance and involves a complex assessment of multiple interacting variables. Several new cardio-pulmonary biomarkers have emerged as strong predictors of risk among PH patients.
Tissue remodeling in pulmonary hypertension is accompanied by structural and functional changes in the myocardial, pulmonary and vascular wall extracellular matrix . The fibrotic changes in heart and lung tissue are controlled by the activity of proteolytic enzymes, such as the extracellular matrix degrading metalloproteinases (ECM MMPs), MMPs can stimulate the secretion of tenascin-C which is upregulated upon tissue injury and is involved in the process of tissue remodeling. It suppresses apoptosis and promotes proliferation of smooth muscle cells.
In the context of pulmonary hypertension, elevated levels are likely to reflect the underlying compensatory tissue remodeling of the cardiopulmonary vasculature. Hence, elevated levels of tenascin-C in patients with pulmonary hypertension may underline the severity of the disease.
The aim of this study was to assess the clinical utility of serum tenascin-c in patients with pulmonary hypertension and to detect its correlation with cardiovascular remodeling, in order to explore its potential prognostic utility in those patients.
This study was conducted on 35 patients suffering from PH; 7 with WHO class 1, 13 with WHO class 2, 6 with WHO class 3& 9 with WHO class 4 and 10 apparently healthy subjects serving as control group. In addition all patients were subdivided according to the severity of the disease into 2 subgroups; subgroup a mild (class 1) & subgroup b moderate to severe (class 2-4).
All studied groups were subjected to history taking and clinical examination. Blood samples were collected for determination of lipid profile, and serum TnC. Assay of TnC were carried using Enzyme Linked Immunosorbant Assay (ELISA).
Significant higher levels of TnC were observed in PH patients when compared to control group. In addition, there was a highly significant increase of TnC levels in PH patients with WHO classes 2 - 4 when compared to control group. Furthermore, a progressive increase in TnC levels where recorded throughout WHO classes 1- 4 and the results recorded in class 4 was significantly higher than classes 1, 2&3.
When ROC curve analysis was applied to asses diagnostic performance of serum TnC in PH patients versus healthy control group, it revealed at a cut-off 0.3 ng/ml the diagnostic sensitivity was 91.4%, the diagnostic specificity was 100%,positive predictive value(PPV) 76.9%, negative predictive value(NPV) 100% and diagnostic efficacy 93.3%.
In addition diagnostic performance of TnC in differences between subgroup Ib(with tissue remodeling) and subgroup Ia (without tissue remodeling) was done by a ROC curve analysis, it revealed at a cut-off 4.3 ng/ml the diagnostic sensitivity was 89.3%, the diagnostic specificity was 85.7%,positive predictive value(PPV) 96.2%, negative predictive value(NPV) 66.7% and diagnostic efficacy 88.6%.
In conclusion, serum tenascin-c (TnC) is a promising diagnostic marker for identifying patients with tissue remodeling in PH. In addition, it is proposed as a useful indicator of disease progression and severity. It can also be used as a potential marker to detect beneficial effects of pharmacotherapy with anti remodeling drugs.