The good and the bad collagens of fibrosis - Their role in signaling and organ function.

Usually the dense extracellular structure in fibrotic tissues is described as extracellular matrix (ECM) or simply as collagen. However, fibrosis is not just fibrosis, which is already exemplified by the variant morphological characteristics of fibrosis due to viral versus cholestatic, autoimmune or toxic liver injury, with reticular, chicken wire and bridging fibrosis. Importantly, the overall composition of the ECM, especially the relative amounts of the many types of collagens, which represent the most abundant ECM molecules and which centrally modulate cellular functions and physiological processes, changes dramatically during fibrosis progression. We hypothesize that there are good and bad collagens in fibrosis and that a change of location alone may change the function from good to bad. Whereas basement membrane collagen type IV anchors epithelial and other cells in a polarized manner, the interstitial fibroblast collagens type I and III do not provide directional information. In addition, feedback loops from biologically active degradation products of some collagens are examples of the importance of having the right collagen at the right place and at the right time controlling cell function, proliferation, matrix production and fate. Examples are the interstitial collagen type VI and basement membrane collagen type XVIII. Their carboxyterminal propeptides serve as an adipose tissue hormone, endotrophin, and as a regulator of angiogenesis, endostatin, respectively. We provide an overview of the 28 known collagen types and propose that the molecular composition of the ECM in fibrosis needs careful attention to assess its impact on organ function and its potential to progress or reverse. Consequently, to adequately assess fibrosis and to design optimal antifibrotic therapies, we need to dissect the molecular entity of fibrosis for the molecular composition and spatial distribution of collagens and the associated ECM.

Rheumatic tricuspid valve disease: two-dimensional echocardiographic, hemodynamic, and angiographic correlations.

From March 1977 through April 1982, 2-dimensional echocardiography detected 372 patients with rheumatic mitral valve disease. Of these patients, 23 (6%) had tricuspid valve involvement. Two-dimensional echocardiographic criteria of rheumatic tricuspid valve disease included thickened leaflets with restriction in motion, diastolic doming, and encroachment of the leaflet tips on the ventricular inlet. These criteria provided a sensitivity of 100%, a specificity of 90%, a predictive accuracy of 21%, and a negative predictive value of 100% in diagnosing hemodynamically significant tricuspid stenosis. Hemodynamic variables in patients with rheumatic tricuspid valve disease (Group I) were compared with those in patients with no rheumatic tricuspid disease (Group II). The only significant difference was mean right atrial pressure (15 +/- 7 mm Hg versus 11 +/- 5 mm Hg, p less than 0.02). Both groups were classified into patients with (A) and without (B) significant tricuspid regurgitation (TR). There was no significant difference in any hemodynamic variable when Group IA was compared with Group IIA. In addition, there was no difference in any hemodynamic variable when patients with functional TR (Group IIA) were compared with those with rheumatic mitral valvular disease without TR (Group IIB). Two-dimensional echocardiography and cardiac catheterization provide complementary diagnostic information in these patients.