Pericardial interstitial cell senescence responsible for pericardial structural remodeling in idiopathic and postsurgical constrictive pericarditis
Idiopathic and postsurgical constrictive pericarditis is characterized by pericardial structural remodeling that involves fibrosis, calcification, and inflammation. This study aimed to determine whether cell senescence was responsible for pericardial structural remodeling.Methods:
Pericardial interstitial cells derived from patients with idiopathic or postsurgical pericarditis (pericarditis cells) were harvested. Timing of senescence and differences in telomere length were compared between age- and sex-matched controls (nonpericarditis cells). Pericardial interstitial cells derived from normal pericardia were serially passaged until senescence (senescent cells). Apoptosis, collagen matrix, calcium deposition, chemoattractant properties, gene expression profiles, and paracrine effects of senescent cells were compared with nonsenescent cells of passage 2 (nonsenescent cells).Results:
Pericarditis cells displayed senescent changes, including short telomere length, large flattened cell sizes, positive staining for senescence-associated β-galactosidase, and limited growth capacity. These senescent cells were resistant to apoptosis, produced more collagen matrix, deposited more calcium, and attracted more monocytes/lymphocytes than the nonsenescent cells. A cluster of genes involved in extracellular matrix deposition (connective tissue growth factor, fibronectin, collagen type I, collagen type III, and tissue inhibitors of metalloproteinase-1), calcium deposition (osteopontin, bone sialoprotein, osteonectin, and matrix Gla protein), and inflammatory cell recruitment (interleukin-6, chemoattractant protein-1, and tumor necrosis factor-α) were upregulated in senescent cells, whereas extracellular matrix-degrading enzyme (metalloproteinase-1 and metalloproteinase-3) was downregulated. Furthermore, senescent cells had the ability to promote the proliferation, differentiation, and senescence of neighboring cells.Conclusions:
These findings suggest that senescent cells have characteristics promoting pericardial structural remodeling, but further work is needed to establish causation.