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Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
Published on: September 15, 2017
Inflammatory Burden and Immunomodulative Therapeutics of Cardiovascular Diseases
Ting-Wei Kao1, Chin-Chou Huang2,3,4,5
1Department of Internal Medicine, National Taiwan University Hospital, Taipei 100225, Taiwan.
Insights
Inflammation significantly impacts cardiovascular diseases like atherosclerosis. Targeting inflammatory pathways and the gut microbiome offers new therapeutic strategies for heart conditions.
Area of Science:
- Cardiovascular Medicine
- Immunology
- Microbiome Research
Background:
- Cardiovascular diseases (CVDs) require understanding beyond traditional risk factors.
- A high inflammatory burden is increasingly recognized as a key driver in CVD pathogenesis and progression, including atherosclerosis and myocardial infarction.
Purpose of the Study:
- To elucidate the mechanistic links between inflammation and cardiovascular diseases.
- To explore novel therapeutic avenues targeting inflammatory pathways and the gut microbiome for CVD management.
Main Methods:
- Investigated signaling pathways downstream of Toll-like receptors, nucleotide oligomerization domain-like receptors, interleukins, and tumor necrosis factor.
- Examined the roles of oxidative stress and ferroptosis.
- Reviewed current and emerging pharmaceutical interventions and the gut-cardio-renal axis.
Main Results:
- Inflammation, oxidative stress, and ferroptosis are central to CVD development.
- Pharmaceuticals like statins and colchicine demonstrate anti-inflammatory cardiovascular benefits.
- Interleukin antagonists and gut microbiome modulation show promise in recent trials.
Conclusions:
- Understanding the inflammatory mechanisms and gut microbiome's role is crucial for CVD treatment.
- Future research leveraging artificial intelligence and machine learning can identify new therapeutic targets for holistic cardiovascular care.
Abstract:
Phenotyping cardiovascular illness and recognising heterogeneities within are pivotal in the contemporary era. Besides traditional risk factors, accumulated evidence suggested that a high inflammatory burden has emerged as a key characteristic modulating both the pathogenesis and progression of cardiovascular diseases, inclusive of atherosclerosis and myocardial infarction. To mechanistically elucidate the correlation, signalling pathways downstream to Toll-like receptors, nucleotide oligomerisation domain-like receptors, interleukins, tumour necrosis factor, and corresponding cytokines were raised as central mechanisms exerting the effect of inflammation. Other remarkable adjuvant factors include oxidative stress and secondary ferroptosis. These molecular discoveries have propelled pharmaceutical advancements. Statin was suggested to confer cardiovascular benefits not only by lowering cholesterol levels but also by attenuating inflammation. Colchicine was repurposed as an immunomodulator co-administered with coronary intervention. Novel interleukin-1β and -6 antagonists exhibited promising cardiac benefits in the recent trials as well. Moreover, manipulation of gut microbiota and associated metabolites was addressed to antagonise inflammation-related cardiovascular pathophysiology. The gut-cardio-renal axis was therein established to explain the mutual interrelationship. As for future perspectives, artificial intelligence in conjunction with machine learning could better elucidate the sequencing of the microbiome and data mining. Comprehensively understanding the interplay between the gut microbiome and its cardiovascular impact will help identify future therapeutic targets, affording holistic care for patients with cardiovascular diseases.
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