The Role of Inflammation in Cardiac Disease: Novel Anti-inflammatory Therapies

Silvius Stephens^*
*Correspondence: Silvius Stephens, Department of Cardiology, University of Brasília, UnB - Brasília, Brasilia - Federal District, 70910-900, Brazil, Email:

Keywords

Hypertension • Chronic inflammation • Myocardial infarction

Introduction

Inflammation is a complex biological response to harmful stimuli, such as pathogens, damaged cells, or irritants, aimed at removing the injurious agent and initiating tissue repair. However, when inflammation becomes chronic or dysregulated, it can exacerbate tissue damage and contribute to the development of various diseases, including those affecting the cardiovascular system. In the context of cardiac disease, inflammation is implicated at multiple stages, from the formation of atherosclerotic plaques to the progression of myocardial injury and remodeling in HF. In atherosclerosis, for example, the accumulation of lipids and immune cells within the arterial wall triggers an inflammatory cascade, leading to plaque formation and eventual rupture, precipitating acute cardiovascular events such as myocardial infarction and stroke.

One such class of agents showing promise in clinical trials is interleukin-1 inhibitors. IL-1 is a key mediator of inflammation implicated in atherosclerosis, myocardial infarction, and HF. Drugs targeting the IL-1 pathway, such as canakinumab and anakinra, have demonstrated beneficial effects in reducing cardiovascular events and improving outcomes in high-risk patients, independent of lipid lowering. Similarly, other anti-inflammatory agents, including colchicine and methotrexate, traditionally used in the treatment of inflammatory conditions such as gout and rheumatoid arthritis, have shown efficacy in reducing cardiovascular events and inflammation markers in clinical studies. These agents exert their effects through various mechanisms, such as inhibition of leukocyte activation and cytokine production, highlighting the diverse targets for anti-inflammatory therapy in cardiac disease [1-3].

Literature Review

Atherosclerosis, the underlying cause of coronary artery disease, involves the buildup of plaque within the arterial walls. This process is driven by inflammation, initiated by the infiltration of immune cells such as macrophages and T lymphocytes into the vessel wall in response to endothelial injury. These inflammatory cells promote the oxidation of low-density lipoprotein cholesterol, leading to the formation of foam cells and the development of fatty streaks. Over time, these lesions progress to more advanced plaques characterized by the deposition of collagen, smooth muscle proliferation, and calcification, ultimately leading to plaque instability and rupture.

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids, immune cells, and cellular debris within the walls of arteries. This process begins with endothelial dysfunction, which occurs when the endothelial cells lining the inner surface of blood vessels become damaged or dysfunctional due to various factors such as high cholesterol levels, hypertension, smoking, and diabetes. Endothelial dysfunction leads to the recruitment of circulating monocytes into the arterial wall. These monocytes then differentiate into macrophages, which engulf oxidized lowdensity lipoprotein particles, becoming foam cells. Foam cells are a hallmark of early atherosclerotic lesions known as fatty streaks. Additionally, endothelial dysfunction promotes the expression of adhesion molecules and chemokines, which further attract immune cells to the site of injury.

As the atherosclerotic lesion progresses, smooth muscle cells from the arterial wall migrate into the intima and proliferate, contributing to the formation of a fibrous cap over the lipid-rich core. This fibrous cap is composed of collagen, elastin, and smooth muscle cells, and its stability is crucial for preventing plaque rupture and thrombosis. The rupture of a vulnerable plaque exposes its thrombogenic core to the bloodstream, leading to the formation of a thrombus (blood clot) that can partially or completely occlude the artery. If the affected artery supplies blood to the heart (coronary artery), this can result in a myocardial infarction (heart attack).

Discussion

The rupture of vulnerable atherosclerotic plaques triggers acute cardiovascular events such as myocardial infarction and stroke. Inflammatory mediators, including interleukin-1β and tumor necrosis factor-alpha, play a central role in this process by promoting endothelial dysfunction, platelet activation, and thrombus formation. Moreover, inflammation contributes to the expansion of the infarct size and the development of adverse remodeling in the aftermath of acute myocardial injury. Inflammation plays a critical role in the development and progression of acute cardiovascular events such as myocardial infarction (heart attack) and stroke. These events are often precipitated by the rupture of vulnerable atherosclerotic plaques within the walls of arteries, leading to the formation of blood clots (thrombi) that can partially or completely obstruct blood flow to vital organs such as the heart or brain.

The rupture of an atherosclerotic plaque triggers a cascade of inflammatory responses within the arterial wall and the bloodstream. One of the key players in this process is the endothelium, the layer of cells that lines the inner surface of blood vessels. Endothelial dysfunction, characterized by impaired vascular homeostasis and increased permeability, is an early event in atherosclerosis and promotes the recruitment of inflammatory cells to the site of plaque rupture. In response to endothelial injury, circulating monocytes adhere to the damaged endothelium and migrate into the subendothelial space, where they differentiate into macrophages. These macrophages phagocytose oxidized low-density lipoprotein particles, leading to the formation of foam cells and the progression of the atherosclerotic lesion [4-6].

Within the plaque, inflammatory cells such as macrophages and T lymphocytes secrete pro-inflammatory cytokines such as interleukin-1β and tumor necrosis factor-alpha. These cytokines amplify the inflammatory response, further promoting the recruitment of immune cells and the activation of endothelial cells and smooth muscle cells within the plaque. In addition to local inflammation within the arterial wall, systemic inflammation also plays a significant role in acute cardiovascular events. Elevated levels of circulating inflammatory markers such as C-reactive protein and interleukin-6 are associated with an increased risk of cardiovascular events and are predictive of adverse outcomes in patients with acute coronary syndromes.

Inflammatory mediators released from the ruptured plaque, such as tissue factor and von Willebrand factor, promote platelet activation and aggregation, leading to the formation of a thrombus at the site of plaque rupture. Moreover, inflammatory cytokines can impair the antithrombotic properties of the endothelium, further promoting thrombosis. The formation of a thrombus can partially or completely occlude the affected artery, resulting in ischemia (lack of blood flow) and tissue injury. In the coronary arteries, this can lead to myocardial infarction, characterized by chest pain, shortness of breath, and electrocardiographic changes indicative of myocardial ischemia or necrosis. In the cerebral arteries, it can result in a stroke, causing neurological deficits such as weakness, speech impairment, and visual disturbances.

Recognizing the detrimental effects of inflammation on cardiovascular health has prompted the development of novel anti-inflammatory therapies to complement traditional approaches. Among these, interleukin-1 inhibitors have shown promising results in clinical trials. Canakinumab, a monoclonal antibody targeting IL-1β, demonstrated a significant reduction in cardiovascular events in patients with a history of myocardial infarction and elevated inflammatory markers, independent of lipid lowering. Similarly, anakinra, an IL-1 receptor antagonist, has shown efficacy in reducing inflammation and improving endothelial function in patients with HF.

Other agents targeting inflammation in cardiovascular disease include colchicine, a microtubule-disrupting agent with anti-inflammatory properties, and methotrexate, an immunosuppressive drug. Clinical studies have shown that these agents can reduce cardiovascular events and inflammation markers in patients with CAD and HF, providing further evidence for the role of inflammation in cardiac disease pathogenesis. Moving forward, ongoing research efforts are focused on elucidating the mechanisms underlying inflammation in cardiac disease and identifying novel therapeutic targets. Advances in precision medicine, including the use of biomarkers and genetic profiling, may enable tailored anti-inflammatory therapies based on individual patient characteristics and disease phenotypes. Moreover, innovative approaches such as targeted drug delivery systems and gene editing technologies hold promise for enhancing the efficacy and safety of antiinflammatory treatments in cardiovascular disease.

Inflammation plays a central role in the pathogenesis of cardiac disease, contributing to atherosclerosis, acute cardiovascular events, and heart failure. Novel anti-inflammatory therapies offer the potential to complement existing treatment strategies and improve outcomes for patients with cardiovascular disease. By targeting inflammatory pathways, these innovative approaches may herald a new era of precision medicine in cardiology, ultimately reducing the burden of cardiovascular morbidity and mortality worldwide.

Conclusion

Inflammation occupies a central role in the pathogenesis of cardiac disease, contributing to atherosclerosis, myocardial injury, and heart failure. The development of novel anti-inflammatory therapies represents a significant advancement in cardiovascular medicine, offering the potential to complement existing treatment strategies and improve outcomes for patients with CVD. By targeting inflammatory pathways, these innovative approaches hold promise for reducing the burden of cardiovascular disease and ushering in a new era of precision medicine in cardiology.

Acknowledgement

None.

Conflict of Interest

Authors declare no conflict of interest.

References

1. Qureshi, Rabail, Leo Kao and Rakesh P. Gupta. "Coronary artery fistula with associated Takotsubo cardiomyopathy: A case report." J Med Case Rep 12 (2018): 1-4.

   Google Scholar, Crossref, Indexed at

2. Kromhout, D., A. A. E. Wibowo, R. F. M. Herber and L. M. Dalderup, et al. "Trace metals and coronary heart disease risk indicators in 152 elderly men (the Zutphen study)." Am J Epidemiol 122 (1985): 378-385.

   Google Scholar, Crossref, Indexed at

3. Fronczek, Martyna, Joanna Katarzyna Strzelczyk, Tadeusz Osadnik and Krzysztof Biernacki, et al. "VDR gene polymorphisms in healthy individuals with family history of premature coronary artery disease." Dis Markers 2021 (2021): 1-9.

   Google Scholar, Crossref, Indexed at

4. Yan, Xiaofei, Yuzhen Wei, Dan Wang and Jiangtao Zhao, et al. "Four common vitamin D receptor polymorphisms and coronary artery disease susceptibility: A trial sequential analysis." Plos one 17 (2022): e0275368.

   Google Scholar, Crossref, Indexed at

5. Yun, Gabin, Tae Hyun Nam and Eun Ju Chun. "Coronary artery fistulas: Pathophysiology, imaging findings and management." Radiographics 38 (2018): 688-703.

   Google Scholar, Crossref, Indexed at

6. Dadkhah-Tirani, Heidar, Arsalan Salari, Shora Shafighnia and Seyed Fazel Hosseini, et al. "Coronary artery to pulmonary artery fistula." Am J Case Rep 14 (2013): 486.

   Google Scholar, Crossref, Indexed at