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. 2021 Mar 30;65(3):245–258. doi: 10.1165/rcmb.2021-0091TR

Table 2.

Function and Expression/Involvement of BM-associated ECM Proteins in the Heart

BM-associated ECM Protein Parent Protein Function Expression/Involvement in Heart Disease
Endostatin Proteolytic cleavage product of collagen type XVIII α1 chain (50)
  • Shows antiangiogenic activity (50)

  • Maintains integrity and stability of BM (12)

  • Circulating elevated endostatin levels in patients with PAH are associated with worsened cardiac function and poor survival (50)

  • Acts as a positive regulator of thrombospondin 1 and is associated with PAH severity (51)

  • Stimulates proliferation, migration, and wound healing in rat cardiac fibroblasts (177, 178)

  • In patients with chronic heart failure and coronary heart disease, increased circulating levels may predict adverse outcomes (172, 179)

  • Rise in endostatin may reflect adverse cardiac remodeling (180)

Endorepellin Cleavage fragment of perlecan from its C-terminal domain by proteolytic enzyme cathepsin L (12, 181, 182)
  • Antiangiogenic, antiapoptotic, and profibrogenic in function (12)

  • Maintains integrity and stability of BM (12)

  • Upregulated levels of cathepsin L have been reported in rats exposed to hypoxia and in the endothelium of patients with IPAH with BMPR2 mutations (183)

  • Marked expression in ischemic reperfusion injury under mild hypothermic conditions in pigs may contribute to an increased structural remodeling of the myocardial BM with potential functional impairment (184)

Arresten Cleavage product of collagen type IV α1 chain by MT1-MMP and MT2-MMP (177)
  • Antiangiogenic and proapoptotic in function (185186)

  • Maintains integrity and stability of BM (12)

  • Antiangiogenic action by inhibiting proliferation and migration, promoting apoptosis in endothelial cells (186), and suppressing the migration and invasion of tumor cells (187)

  • Increased expression in ischemic reperfusion injury under mild hypothermic conditions in pigs may contribute to an increased structural remodeling of the myocardial BM with potential functional impairment (184)

Canstatin Fragment derived from α2 chain of collagen type IV by MT1-MMP and MT2-MMP (177)
  • Potent antiangiogenic factor (188)

  • Maintains integrity and stability of BM (12)

  • Increased degradation by cathepsin S at the site of infarcted area after myocardial infarction may be involved in the pathogenesis of myocardial infarction through increased turnover (188)

  • Stimulates the migration of rat cardiac fibroblasts through the increased expression of MMP2 (189)

  • Inhibits hypoxia-induced apoptosis in H9c2 cardiomyoblasts (190)

Tumstatin Cleavage fragment of collagen type IV α3 chain (191)
  • Exhibits both antiangiogenetic and antitumor properties (191)

  • Maintains integrity and stability of BM (12)

  • Increased expression following cardiac pressure overload stimulates the proliferation and migration of cardiac fibroblasts and may play a profibrotic role (191)

Thrombospondin 1 N/A
  • Shows potent antiangiogenic activity (192)

  • Stabilizes the ECM (193)

  • Increased protein expression stimulates pulmonary endothelial cell apoptosis, inhibits migration and proliferation, and conversely promotes smooth muscle cell proliferation (51)

  • Increased expression promotes fibrosis and diminished cardiac function in the diabetic pressure overloaded heart (194)

  • Elevated plasma levels in PH cohort correlate with increased mortality (195)

Thrombospondin 2 N/A
  • Preserves the integrity of the cardiac ECM (196, 197)

  • Overexpression leads to progression of heart failure (196)

  • Increased expression reflects disease severity and predicts adverse outcomes (198)

Definition of abbreviations: BM = basement membrane; ECM = extracellular matrix; IPAH = idiopathic PAH; N/A  =  not applicable; PAH  =  pulmonary arterial hypertension; PH  =  pulmonary hypertension.