Increased collagen deposition and elevated expression of connective tissue growth factor in human thoracic aortic dissection

Circulation. 2006 Jul 4;114(1 Suppl):I200-5. doi: 10.1161/CIRCULATIONAHA.105.000240.

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 (n=10) and controls (n=10) 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 (P<0.05 for all). Similar patterns were shown in mRNA levels of type Ialpha and Ialpha2 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 506+/-108 counts per minute to 2764+/-240 cpm by 50 ng/mL CTGF, and from 30+/-43 cpm to 429+/-102 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. Because CTGF can increase collagen expression, CTGF may be a new target molecule in the pathogenesis and progression of TAD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aneurysm, Dissecting / genetics
  • Aneurysm, Dissecting / metabolism*
  • Aneurysm, Dissecting / pathology
  • Aorta, Thoracic / metabolism
  • Aorta, Thoracic / pathology
  • Aortic Aneurysm, Thoracic / genetics
  • Aortic Aneurysm, Thoracic / metabolism*
  • Aortic Aneurysm, Thoracic / pathology
  • Apoptosis
  • Collagen Type I / biosynthesis*
  • Collagen Type I / genetics
  • Collagen Type III / biosynthesis*
  • Collagen Type III / genetics
  • Compliance
  • Connective Tissue Growth Factor
  • Female
  • Gene Expression Profiling
  • Humans
  • Immediate-Early Proteins / biosynthesis
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / pharmacology
  • Immediate-Early Proteins / physiology*
  • Intercellular Signaling Peptides and Proteins / biosynthesis
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Male
  • Middle Aged
  • Muscle, Smooth, Vascular / pathology
  • Recombinant Proteins / pharmacology

Substances

  • CCN2 protein, human
  • Collagen Type I
  • Collagen Type III
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • Recombinant Proteins
  • Connective Tissue Growth Factor