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Reprogramming of the lipid metabolism axis in systemic sclerosis: mechanism analysis and therapeutic potential
Rong-Hong Guo1, Xian-Zhe Zhou1, Yan-Li Yang1
1Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China.
Abstract:
Systemic sclerosis (SSc), a highly fatal autoimmune disease, is characterized by pathological hallmarks including microvascular damage, immune dysregulation, and progressive fibrosis affecting the skin and multiple organs. Clinically, SSc-related interstitial lung disease and cardiovascular complications represent the primary causes of mortality. Emerging research has highlighted the role of lipid metabolism dysregulation in SSc pathogenesis, with clinically observed abnormal lipid profiles potentially linked to disease progression. Advances in lipidomics have elucidated pathological alterations in specific lipid species and their signaling pathways, offering novel insights into metabolic reprogramming in SSc and identifying potential therapeutic targets. This review synthesizes current evidence on lipid abnormalities in SSc patients, focusing on the interplay between dyslipidemia and three core pathological processes: vascular injury, immune dysfunction, and fibrotic remodeling. Additionally, we briefly analyze the effects of existing drug interventions on the lipid profile of SSc patients, providing a foundation for developing lipid metabolism-targeted therapies to refine clinical management.
Insights
Systemic sclerosis (SSc) involves lipid metabolism issues, impacting vascular injury, immune dysfunction, and fibrosis. Understanding these lipid abnormalities offers new therapeutic targets for this autoimmune disease.
Area of Science:
- Immunology
- Metabolic disorders
- Cardiovascular medicine
Background:
- Systemic sclerosis (SSc) is a fatal autoimmune disease with vascular damage, immune dysregulation, and fibrosis.
- SSc-related interstitial lung disease and cardiovascular complications are leading causes of mortality.
- Lipid metabolism dysregulation is increasingly recognized in SSc pathogenesis.
Purpose of the Study:
- To review current evidence on lipid abnormalities in SSc patients.
- To explore the interplay between dyslipidemia and SSc pathology (vascular injury, immune dysfunction, fibrosis).
- To analyze the impact of existing drugs on SSc lipid profiles and inform targeted therapies.
Main Methods:
- Literature review synthesizing current research on lipidomics in SSc.
- Analysis of pathological hallmarks and their connection to lipid metabolism.
- Evaluation of drug effects on lipid profiles in SSc patients.
Main Results:
- Lipidomics reveals pathological alterations in specific lipid species and signaling pathways in SSc.
- Dyslipidemia is linked to vascular injury, immune dysfunction, and fibrotic remodeling in SSc.
- Existing drug interventions show variable effects on SSc lipid profiles.
Conclusions:
- Lipid metabolism dysregulation is a key factor in SSc pathogenesis.
- Targeting lipid metabolism presents a promising therapeutic strategy for SSc.
- Further research is needed to refine lipid metabolism-targeted therapies for SSc management.
