Inflammatory Burden and Immunomodulative Therapeutics of Cardiovascular Diseases

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.

Colchicine in atherosclerotic coronary artery disease: new challenges for an old drug

“…Although cardiac enzyme levels and infarct size by cardiac magnetic resonance imaging were significantly reduced (p=0.019), there was no reduction in adverse events. These results suggest a potential benefit of colchicine in AMI with ST -segment elevation (SLOBODNICK et al, 2018;TUCKER et al, 2021;KAO;HUANG, 2022).…”

“…A retrospective study that evaluated 7,026 individuals after the intervention proposed that high levels of C-Reactive Protein (CRP) were correlated with all-cause mortality and the risk of AMI. A pioneering study demonstrated that colchicine can prevent elevation of biomarkers in an acute coronary event, as it suppressed the increase in IL-6 and CRP concentrations after coronary angioplasty (SHA et al, 2020;KAO;HUANG, 2022).…”

“…Cardiovascular event rates were 5.5% in the colchicine group and 7.1% in the placebo group (p = 0.02). (JIA et al, 2020;TUCKER et al, 2021;KAO;HUANG, 2022).…”

Identification of biomarkers and therapeutic targets in the peripheral immune landscape from coronary artery disease

“…Notably, in this study, some traditionally considered risk genes and cell subsets of CAD patients did not enter our candidate team, such as CRP, MCP-1, monocytes, etc. We speculated that these patients might be related to statins or other therapeutic drugs, which have proved to be signi cantly changed the immune characteristics in peripheral blood [51].…”

Editorial of Special Issue “The Interplay of Microbiome and Immune Response in Health and Diseases—2nd Edition”

“…The inflammation/immunity-microbiota axis is also evaluated by the manuscript of Ting-Wei Kao focused on cardiovascular diseases [7]. An increased inflammatory status has recently been proposed as an independent risk factor for developing end-organ comorbidities and adverse prognoses of various chronic illnesses [8].…”