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New Insights into Immunity and Inflammation in Cardiovascular Diseases
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New Insights into Immunity and Inflammation in Cardiovascular Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: 20 July 2026 | Viewed by 20888

Special Issue Editor

Dr. David J. Vigerust

E-Mail Website
Guest Editor
School of Medicine, Vanderbilt University, Nashville, TN, USA
Interests: innate immunity; infectious disease; cardiovascular disease; neurodegeneration

Special Issue Information

Dear Colleagues,

Cardiovascular diseases are the leading cause of morbidity and mortality around the world, and represent a significant burden to society and the economy. Accumulating evidence has demonstrated a clear connection between the immune system and the entire spectrum of cardiovascular disease. Studies in recent years have illustrated the critical role that immunity and inflammation play in the development and progression of cardiovascular diseases. These findings have led to a greater understanding of the role of the innate and adaptive immune systems in CVDs, but critical gaps remain in our understanding. Of special interest is the role of cytokines and chemokines, infectious agents, chronic inflammation, and oxidative stress in the development of cardiovascular disease. To address these gaps, the International Journal of Molecular Sciences has launched a Special Issue and is seeking submissions on the topic of “New Insights into Immunity and Inflammation in Cardiovascular Diseases”.

Dr. David J. Vigerust
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • pathogens
  • oxidative stress
  • cytokines
  • chemokines
  • immunity
  • chronic inflammation

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Published Papers (6 papers)

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Research

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17 pages, 1356 KB  
Article
New Biomarkers in the Prognostic Assessment of Acute Heart Failure with Reduced Ejection Fraction: Beyond Natriuretic Peptides
by Marcelino Cortés, Jairo Lumpuy-Castillo, Camila Sofía García-Talavera, María Belén Arroyo Rivera, Lara de Miguel, Antonio José Bollas, Jose Maria Romero-Otero, Jose Antonio Esteban Chapel, Mikel Taibo-Urquía, Ana María Pello, María Luisa González-Casaus, Ignacio Mahíllo-Fernández, Oscar Lorenzo and José Tuñón
Int. J. Mol. Sci. 2025, 26(3), 986; https://doi.org/10.3390/ijms26030986 - 24 Jan 2025
Cited by 7 | Viewed by 3461
Abstract
Natriuretic peptides are established biomarkers related to the prognosis of heart failure. New biomarkers have emerged in the field of cardiovascular disease. The prognostic value of these biomarkers in heart failure with reduced left ventricular ejection fraction is not well-established. We conducted a [...] Read more.
Natriuretic peptides are established biomarkers related to the prognosis of heart failure. New biomarkers have emerged in the field of cardiovascular disease. The prognostic value of these biomarkers in heart failure with reduced left ventricular ejection fraction is not well-established. We conducted a prospective, single-centre study, including (July 2019 to March 2023) 104 patients being consecutively admitted with a diagnosis of acute heart failure with reduced ejection fraction decompensation. The median follow-up was 23.5 months, during which 20 deaths (19.4%) and 21 readmissions for heart failure (20.2%) were recorded. Plasma biomarkers, such as NT-proBNP, GDF-15, sST2, suPAR, and FGF-23, were associated with an increased risk of all-cause mortality. However, a Cox regression analysis showed that the strongest predictors of mortality were an estimated glomerular filtration rate (HR 0.96 [0.93–0.98]), GDF-15 (HR 1.3 [1.16–1.45]), and sST2 (HR 1.2 [1.11–1.35]). The strongest predictive model was formed by the combination of the glomerular filtration rate and sST2 (C-index 0.758). In conclusion, in patients with acute decompensated heart failure with reduced ejection fraction, GDF-15 and sST2 showed the highest predictive power for all-cause mortality, which was superior to other established biomarkers such as natriuretic peptides. GDF-15 and sST2 may provide additional prognostic information to improve the prognostic assessment. Full article
(This article belongs to the Special Issue New Insights into Immunity and Inflammation in Cardiovascular Diseases)
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Review

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12 pages, 1119 KB  
Review
Exploring the Clinical Utility of Osteoprotegerin in Heart Failure—A Systematic Review and Meta-Analysis
by Gifar Gazi, Gabi Gazi, Robert Cristian Cruciat, Daniel-Corneliu Leucuta, Stefan-Lucian Popa and Abdulrahman Ismaiel
Int. J. Mol. Sci. 2025, 26(22), 11053; https://doi.org/10.3390/ijms262211053 - 15 Nov 2025
Viewed by 666
Abstract
Osteoprotegerin (OPG) is a glycoprotein involved in bone metabolism and cardiovascular health, with emerging evidence suggesting its role in heart failure (HF). Despite its potential as a biomarker, the association between circulating OPG levels and HF severity remains unclear. This systematic review and [...] Read more.
Osteoprotegerin (OPG) is a glycoprotein involved in bone metabolism and cardiovascular health, with emerging evidence suggesting its role in heart failure (HF). Despite its potential as a biomarker, the association between circulating OPG levels and HF severity remains unclear. This systematic review and meta-analysis aimed to evaluate OPG levels in HF patients and their relationship with disease severity according to the New York Heart Association (NYHA) classification. A comprehensive search of PubMed, EMBASE, and Scopus was conducted to identify observational studies assessing OPG levels in HF patients. Studies were included if they reported OPG levels in HF patients and controls, with subgroup analyses according to NYHA classification when available. Risk of bias assessment was performed using the Newcastle–Ottawa Scale (NOS). The principal outcome was the mean difference (MD) in circulating OPG levels between HF patients and controls. Random-effects meta-analysis models were used to pool the data. Thirteen studies with a total of 1387 participants were included in the quantitative and qualitative synthesis. Overall, OPG levels were significantly elevated in HF patients compared to healthy controls (2.490 [95% CI 0.531, 4.449]). Subgroup analysis showed a significant decrease in OPG levels in controls versus NYHA II patients (−1.503 [95% CI −2.402, −0.604]). However, no statistically significant difference was found when comparing OPG levels between the combined NYHA II/III group and controls (−1.019 [95% CI −2.451, 0.412]). OPG levels are significantly elevated in HF patients compared to controls, with a progressive increase in NYHA II patients. However, the lack of significance in the NYHA II/III group highlights the need for further studies with a more comprehensive NYHA classification breakdown. Full article
(This article belongs to the Special Issue New Insights into Immunity and Inflammation in Cardiovascular Diseases)
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21 pages, 823 KB  
Review
Inflammasomes in Cardiovascular Diseases: Current Knowledge and Future Perspectives
by Mario Caldarelli, Laura Franza, Sebastiano Cutrupi, Martina Menegolo, Francesco Franceschi, Antonio Gasbarrini, Giovanni Gambassi and Rossella Cianci
Int. J. Mol. Sci. 2025, 26(12), 5439; https://doi.org/10.3390/ijms26125439 - 6 Jun 2025
Cited by 9 | Viewed by 3137
Abstract
Chronic inflammation is an important contributor to the development of cardiovascular disorders, and inflammasomes, especially the NOD-like receptor protein 3 (NLRP3), are emerging as crucial mediators in this context. Inflammasomes are activated through receptor-mediated danger signals, such as cholesterol crystals and cellular damage [...] Read more.
Chronic inflammation is an important contributor to the development of cardiovascular disorders, and inflammasomes, especially the NOD-like receptor protein 3 (NLRP3), are emerging as crucial mediators in this context. Inflammasomes are activated through receptor-mediated danger signals, such as cholesterol crystals and cellular damage products, thereby stimulating the secretion of pro-inflammatory cytokines, which sustains inflammation. This mechanism drives atherosclerosis (via plaque formation and destabilization), heart failure (via fibrotic remodeling), and pericarditis (via exacerbation of pericardial inflammation). Therapeutic approaches seek to block inflammasome activation or their pro-inflammatory pathways. Colchicine, interleukin-1 inhibitors (anakinra, canakinumab), and Sodium-Glucose Transport Protein 2 (SGLT2) inhibitors have a positive impact on cardiovascular inflammation. Various new compounds, such as MCC950, have been described as novel specific inhibitors of NLRP3. Further studies are needed to validate the effectiveness and safety of these treatments. Further elucidating the role of inflammasomes in cardiovascular disease could open the way to achieving more effective therapies, allowing for better management of high-risk cardiovascular patients. Full article
(This article belongs to the Special Issue New Insights into Immunity and Inflammation in Cardiovascular Diseases)
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10 pages, 1660 KB  
Review
Leptin Unveiled: A Potential Biomarker for Acute Coronary Syndrome with Implications for Tailored Therapy in Patients with Type 2 Diabetes—Systematic Review and Meta-Analysis
by Abdulrahman Ismaiel, Gaëlle Oliveira-Grilo, Daniel-Corneliu Leucuta, Nahlah Al Srouji, Mohamed Ismaiel and Stefan-Lucian Popa
Int. J. Mol. Sci. 2025, 26(9), 3925; https://doi.org/10.3390/ijms26093925 - 22 Apr 2025
Cited by 1 | Viewed by 1457
Abstract
Several studies evaluated the association between adipokines, including leptin, in patients with acute coronary syndrome (ACS). Nevertheless, the results have been inconclusive and conflicting. Therefore, we assessed the pertinent published studies and evaluated the association between leptin levels and ACS. In January 2023, [...] Read more.
Several studies evaluated the association between adipokines, including leptin, in patients with acute coronary syndrome (ACS). Nevertheless, the results have been inconclusive and conflicting. Therefore, we assessed the pertinent published studies and evaluated the association between leptin levels and ACS. In January 2023, we conducted a comprehensive systematic search using Web of Science, PubMed, Scopus, and Embase. Using the Newcastle–Ottawa Scale, we evaluated the quality of all the articles we included. The principal summary outcome was the mean difference (MD) in leptin levels. We included 16 studies in our systematic review, 10 of which were included in meta-analysis. The MD in leptin levels was then evaluated in each subgroup: the patients with ACS versus the controls, the patients with ACS versus the patients with stable angina pectoris (SAP), and the patients with type 2 diabetes mellitus (T2DM) and ACS versus the patients without diabetes, but with ACS. Respectively, the following MDs were obtained: 10.508 (95% CI 3.670–17.346); 2.408 (95% CI −0.150–4.966); and 17.089 (95% CI 5.565–28.612). The leptin levels were significantly higher in the patients with ACS compared to the healthy controls, as well as in the patients with ACS and T2DM compared to those without T2DM. However, no statistically significant increase in leptin levels was observed when comparing the patients with ACS to those with SAP. Full article
(This article belongs to the Special Issue New Insights into Immunity and Inflammation in Cardiovascular Diseases)
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34 pages, 1439 KB  
Review
The Interplay Between Immunity, Inflammation and Endothelial Dysfunction
by Ying Jie Chee, Rinkoo Dalan and Christine Cheung
Int. J. Mol. Sci. 2025, 26(4), 1708; https://doi.org/10.3390/ijms26041708 - 17 Feb 2025
Cited by 28 | Viewed by 7287
Abstract
The endothelium is pivotal in multiple physiological processes, such as maintaining vascular homeostasis, metabolism, platelet function, and oxidative stress. Emerging evidence in the past decade highlighted the immunomodulatory function of endothelium, serving as a link between innate, adaptive immunity and inflammation. This review [...] Read more.
The endothelium is pivotal in multiple physiological processes, such as maintaining vascular homeostasis, metabolism, platelet function, and oxidative stress. Emerging evidence in the past decade highlighted the immunomodulatory function of endothelium, serving as a link between innate, adaptive immunity and inflammation. This review examines the regulation of the immune–inflammatory axis by the endothelium, discusses physiological immune functions, and explores pathophysiological processes leading to endothelial dysfunction in various metabolic disturbances, including hyperglycemia, obesity, hypertension, and dyslipidaemia. The final section focuses on the novel, repurposed, and emerging therapeutic targets that address the immune–inflammatory axis in endothelial dysfunction. Full article
(This article belongs to the Special Issue New Insights into Immunity and Inflammation in Cardiovascular Diseases)
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27 pages, 3215 KB  
Review
Complement Immune System in Pulmonary Hypertension-Cooperating Roles of Circadian Rhythmicity in Complement-Mediated Vascular Pathology
by Hunter DeVaughn, Haydn E. Rich, Anthony Shadid, Priyanka K. Vaidya, Marie-Francoise Doursout and Pooja Shivshankar
Int. J. Mol. Sci. 2024, 25(23), 12823; https://doi.org/10.3390/ijms252312823 - 28 Nov 2024
Cited by 10 | Viewed by 3906
Abstract
Originally discovered in the 1890s, the complement system has traditionally been viewed as a “compliment” to the body’s innate and adaptive immune response. However, emerging data have shown that the complement system is a much more complex mechanism within the body involved in [...] Read more.
Originally discovered in the 1890s, the complement system has traditionally been viewed as a “compliment” to the body’s innate and adaptive immune response. However, emerging data have shown that the complement system is a much more complex mechanism within the body involved in regulating inflammation, gene transcription, attraction of macrophages, and many more processes. Sustained complement activation contributes to autoimmunity and chronic inflammation. Pulmonary hypertension is a disease with a poor prognosis and an average life expectancy of 2–3 years that leads to vascular remodeling of the pulmonary arteries; the pulmonary arteries are essential to host homeostasis, as they divert deoxygenated blood from the right ventricle of the heart to the lungs for gas exchange. This review focuses on direct links between the complement system’s involvement in pulmonary hypertension, along with autoimmune conditions, and the reliance on the complement system for vascular remodeling processes of the pulmonary artery. Furthermore, circadian rhythmicity is highlighted as the disrupted homeostatic mechanism in the inflammatory consequences in the vascular remodeling within the pulmonary arteries, which could potentially open new therapeutic cues. The current treatment options for pulmonary hypertension are discussed with clinical trials using complement inhibitors and potential therapeutic targets that impact immune cell functions and complement activation, which could alleviate symptoms and block the progression of the disease. Further research on complement’s involvement in interstitial lung diseases and pulmonary hypertension could prove beneficial for our understanding of these various diseases and potential treatment options to prevent vascular remodeling of the pulmonary arteries. Full article
(This article belongs to the Special Issue New Insights into Immunity and Inflammation in Cardiovascular Diseases)
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