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Modified citrus pectin protects aortic dissection development involving macrophage pyroptosis
Chun-Che Shih1, Wei-Lun Lin2, Chih-Pin Chuu3
1Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan; Division of Cardiovascular Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, 11031, Taiwan; Taipei Heart Institute, Taipei Medical University, Taipei, 11031, Taiwan.
Background:
Uncontrolled aortic aneurysms can progress to aortic dissection (AD), a severe vascular disorder characterized by hematoma formation in the aortic wall, with inflammation playing a crucial role. Galectin-3 (Gal-3), a 26-kDa lectin, regulates many aspects of inflammatory cell behavior. Inhibition of Gal-3 ameliorates diabetic neuroinflammation and cardiomyopathy. Modified citrus pectin (MCP) is a PH-modified dietetic supplement produced from citrus pectin. This study investigates the therapeutic potential of MCP, which has a known affinity for Gal-3, in AD.
Methods:
A murine model of AD was induced by β-aminopropionitrile fumarate (BAPN)/angiotensin II (Ang-II) and treated orally with either 100 mg/kg MCP or vehicle. In vitro, H2O2 treatment was applied to RAW264.7 cells to detect macrophage death and pyroptosis.
Results:
MCP administration significantly reduced AD incidence and mortality, with decreased inflammatory cell infiltration in the aorta. MCP downregulated genes associated with inflammation and pyroptosis. In vitro, MCP mitigated macrophage death and pyroptosis induced by H2O2 treatment. The study suggests that MCP's protective effects are due to its interference with the Gal-3 and TLR4 interaction, inhibiting pyroptotic macrophage-induced inflammation.
Conclusion:
MCP could improve patient outcomes and reduce progression to severe forms of AD. Clinically, MCP could serve as supportive therapy to prevent and delay aortic dissection, particularly during the acute stage of uncomplicated type B AD in patients with Marfan syndrome or abdominal aortic aneurysm.
