Increased Collagen Deposition and Elevated Expression of Connective Tissue Growth Factor in Human Thoracic Aortic Dissection

Abstract

Background-Thoracic aortic dissection (TAD) is characterized by dysregulated extracellular matrix. Little is known about the alterations of collagen and stimulators of collagen synthesis, eg, connective tissue growth factor (CTGF), in patients with TAD. In this study, we examined their roles in TAD. Methods and Results-Surgical specimens of the aortic wall of TAD patients (nϭ10) and controls (nϭ10) were tested for collagen types I and III and CTGF expression. When compared with controls, protein levels of type I and III collagen and CTGF were significantly increased by 3.2-, 3.7-, and 5.3-fold, respectively (PϽ0.05 for all). Similar patterns were shown in mRNA levels of type I␣ and I␣2 collagen and CTGF. Using immunohistochemistry and trichrome staining, we also observed elevated levels of collagen in the aortic media and adventitia. Treatment with recombinant human CTGF increased collagen synthesis in cultured aortic smooth muscle cells in a dose-and time-dependent fashion, in which expression of collagens increased from 506Ϯ108 counts per minute to 2764Ϯ240 cpm by 50 ng/mL CTGF, and from 30Ϯ43 cpm to 429Ϯ102 cpm at 48 hours. Conclusions-TAD patients exhibited significantly increased expression of aortic collagen types I and III as well as CTGF, which is likely to be responsible for the compromised aortic distensibility and systemic compliance.

Connective Tissue Growth Factor Transgenic Mouse Develops Cardiac Hypertrophy, Lean Body Mass and Alopecia

“…Adventitial remodeling and thickening is characterised by an increase in Extracellur Matrix (ECM) protein deposition. The previous study revealed the adventitia to be the main site of collagen deposition in the aortic wall [29]. CTGF is known to mediate aortic adventitial fibroblast collagen synthesis stimulated by Angiotensin-II (Ang II) [30] and it is conceivable that, in our study, the hypertrophy and remodeling that we observed in aorta root is directly the result of collagen accumulation in adventitia and the increase in renin synthesis in the aorta root.…”

Inhibition of β-catenin signaling protects against CTGF-induced alveolar and vascular pathology in neonatal mouse lung

“…We also showed that inhibition of β-catenin signaling downregulates CTGF-induced collagen 1a1 expression. Collagen 1a1 is one of the most important ECM that is associated with progressive pulmonary and vascular fibrosis (37). Many studies have demonstrated that CTGF upregulates collagen 1a1 expression in many types of cells including lung fibroblasts and vascular smooth muscle cells.…”

Thrombin induced connective tissue growth factor expression in rat vascular smooth muscle cells via the PAR-1/JNK/AP-1 pathway

“…Overexpression of CTGF has been found in atherosclerotic carotid arteries and in the aortic wall from patient with thoracic aortic dissection [8,44] . Based on the result of this study, together with evidence from clinical specimens, it might suggest that CTGF is one of the mediators in the progression of atherosclerosis [44] . There are many new and emerging antithrombotic agents including PAR-1 antagonists, thrombin inhibitors, etc [45,46] .…”