Adipocyte-released adipomes in Chagas cardiomyopathy: Impact on cardiac metabolic and immune regulation
Hariprasad Thangavel1, Dhanya Dhanyalayam1, Michelle Kim1
1Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA.
Insights
Trypanosoma cruzi infection causes Chagas cardiomyopathy by triggering adipocyte apoptosis and releasing adipomes. These adipomes, particularly plasma-derived infection-associated L-adipomes (P-ILA), drive cardiac inflammation and dysfunction.
Area of Science:
- Immunology
- Cardiology
- Cell Biology
Background:
- Chronic Trypanosoma cruzi infection causes Chagas cardiomyopathy (CCM), a progressive heart disease.
- The precise mechanisms linking T. cruzi infection to CCM pathogenesis, particularly involving adipocyte dysfunction, remain unclear.
Purpose of the Study:
- To investigate the role of adipocyte apoptosis and extracellular vesicles in T. cruzi-induced CCM.
- To characterize adipomes released during infection and their impact on cardiac function.
Main Methods:
- Developed a novel method to isolate adipomes from infected mouse adipose tissue and plasma.
- Analyzed adipome lipid cargo and functional effects on cardiac cells and in vivo models.
- Assessed immunometabolic signaling, adipogenic/lipogenic, and mitochondrial functions.
Main Results:
- T. cruzi infection induces adipocyte apoptosis, releasing extracellular vesicles termed "adipomes".
- Plasma-derived infection-associated L-adipomes (P-ILA) were identified as key mediators, carrying unique lipid cargoes.
- P-ILA treatment induced hypertrophic cardiomyopathy in wild-type mice and exacerbated CCM in infected mice by altering cardiac metabolic pathways.
Conclusions:
- Adipomes, especially P-ILA, are critical effectors in T. cruzi-induced CCM pathogenesis.
- These findings reveal a novel mechanism involving adipocyte-derived extracellular vesicles in cardiac remodeling and inflammation.
- Targeting adipome-mediated pathways may offer new therapeutic strategies for Chagas disease.
Abstract:
Chronic Trypanosoma cruzi infection leads to Chagas cardiomyopathy (CCM), with varying manifestations such as inflammatory hypertrophic cardiomyopathy, arrhythmias, and dilated cardiomyopathy. The factors responsible for the increasing risk of progression to CCM are not fully understood. Previous studies link adipocyte loss to CCM progression, but the mechanism triggering CCM pathogenesis remains unexplored. Our study uncovers that T. cruzi infection triggers adipocyte apoptosis, leading to the release of extracellular vesicles named "adipomes". We developed an innovative method to isolate intact adipomes from infected mice's adipose tissue and plasma, showing they carry unique lipid cargoes. Large and Small adipomes, particularly plasma-derived infection-associated L-adipomes (P-ILA), regulate immunometabolic signaling and induce cardiomyopathy. P-ILA treatment induces hypertrophic cardiomyopathy in wild-type mice and worsens cardiomyopathy severity in post-acute-infected mice by regulating adipogenic/lipogenic and mitochondrial functions. These findings highlight adipomes' pivotal role in promoting inflammation and impairing myocardial function during cardiac remodeling in CD.
