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Biomedicines
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Cardiometabolic Diseases: Molecular Biomarkers and Treatment Strategies
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Cardiometabolic Diseases: Molecular Biomarkers and Treatment Strategies

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Endocrinology and Metabolism Research".

Deadline for manuscript submissions: 31 January 2027 | Viewed by 2097

Editors

Dr. Jelena Radovanović

E-Mail Website
Guest Editor
Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences—National Institute of the Republic of Serbia, University of Belgrade, P.O. Box 522, 11000 Belgrade, Serbia
Interests: cardiology; vascular diseases; endocrinology; diabetes mellitus; igf-1; metabolic syndrome
Dr. Sonja Zafirovic

E-Mail Website
Guest Editor
Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences—National Institute of the Republic of Serbia, University of Belgrade, P.O. Box 522, 11000 Belgrade, Serbia
Interests: cardiovascular diseases; metabolic syndrome; obesity; endocrinology

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to this Special Issue on Cardiometabolic Disease: Molecular Biomarkers and Treatment Strategies in Biomedicines. 

Cardiometabolic disease (CMD) is the leading global cause of human mortality and morbidity worldwide. Development of CMD is a particularly complex pathophysiological condition that involves an unclear network of metabolic and hormonal dysregulation. This compound pathology comprises insulin impairment, alterations in lipid status, hypertension, obesity, and chronic low-grade inflammation. Nevertheless, this is a significant field of medicine that has been at the center of research due to its global prevalence. Clarification of molecular mechanisms and the development of optimized diagnostic and treatment approaches for patients with this condition are essential for achieving a prosperous long-term outcome. Given that traditional biomarkers have certain limitations, for instance, relative sensitivity and reliability in particular clinical circumstances, the management of additional and individual biomarkers and treatment strategies is imperative for present-day medicine. Novel research related to the evaluation of CMD molecular biomarkers is an important topic that could improve timely treatment and enhance positive outcomes. 

This Special Issue aims to highlight biomarkers for CMDs, together with omics technologies and analytical approaches that offer better-quality information for risk assessment, diagnosis, prognosis, and treatment management. In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the recent discoveries related to the use of biomarkers for the advanced management of CMDs. We look forward to receiving your valuable contributions. 

Dr. Jelena Radovanović
Dr. Sonja Zafirovic
Guest Editors

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-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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

  • cardiometabolic disease
  • obesity
  • diabetes mellitus
  • insulin resistance
  • lipid status
  • biomarkers
  • hypertension
  • metabolic dysregulation
  • personalized therapy
  • omics technologies

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Published Papers (4 papers)

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Research

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18 pages, 4567 KB  
Article
Tirzepatide Attenuates Wire Injury-Induced Arterial Remodeling in Non-Diabetic and Diabetic Mice: Comparison with Semaglutide
by Yusaku Mori, Naoya Osaka, Michishige Terasaki, Hironori Yashima, Tomomi Saito, Daiki Tanno, Madoka Ogino, Makoto Ohara and Sho-Ichi Yamagishi
Biomedicines 2026, 14(7), 1554; https://doi.org/10.3390/biomedicines14071554 - 11 Jul 2026
Viewed by 192
Abstract
Background: Glucose-dependent insulinotropic polypeptide receptor (GIPR) and glucagon-like peptide-1 receptor (GLP-1R) activation exert anti-diabetic and anti-obesity effects. Tirzepatide, a dual GIPR/GLP-1R agonist, has demonstrated cardiovascular benefits in clinical studies. However, the direct vascular actions of tirzepatide and their potential advantages over selective [...] Read more.
Background: Glucose-dependent insulinotropic polypeptide receptor (GIPR) and glucagon-like peptide-1 receptor (GLP-1R) activation exert anti-diabetic and anti-obesity effects. Tirzepatide, a dual GIPR/GLP-1R agonist, has demonstrated cardiovascular benefits in clinical studies. However, the direct vascular actions of tirzepatide and their potential advantages over selective GLP-1 receptor agonists (GLP-1RAs) remain unclear. We investigated the vasoprotective effects of tirzepatide and compared them with those of GLP-1 receptor agonists in vivo and in vitro. Methods: Non-diabetic C57BL/6 and diabetic KK-Ay mice received tirzepatide, semaglutide, or vehicle. Arterial remodeling was induced by femoral artery wire injury. A subset of mice was co-treated with the nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME). After 4 weeks, biochemical, morphometric, and immunofluorescence analyses were performed. In vitro, human umbilical vein endothelial cells (HUVECs) were stimulated with tirzepatide or liraglutide to assess nitric oxide (NO) production. Results: In non-diabetic mice, tirzepatide suppressed intimal hyperplasia, including at a low dose that did not affect metabolic parameters, whereas semaglutide had no significant effect on intimal hyperplasia at the same molar dose. The protective effects of tirzepatide were abolished by L-NAME. In diabetic mice, tirzepatide and semaglutide similarly improved metabolic parameters and attenuated intimal hyperplasia. In HUVECs, tirzepatide increased NO production in a dose-dependent manner, and this effect was preserved under hyperglycemic conditions. Tirzepatide and liraglutide induced comparable NO production at equivalent molar concentrations. Conclusions: Tirzepatide, but not semaglutide, exerted vasoprotective effects under non-diabetic conditions in a NO-dependent manner, whereas both agents exhibited comparable vasoprotective effects under diabetic conditions. Full article
(This article belongs to the Special Issue Cardiometabolic Diseases: Molecular Biomarkers and Treatment Strategies)
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14 pages, 786 KB  
Article
In Vitro Evaluation of GLP-1R-Associated Activity of a Sustainable Standardized Phospholipid-Formulated Bergamot Extract
by Amjad Khan, Rosa M. Mella, Patricia Villacé, Meritxell Roura-Ferrer, Jorge Gamiz, Alessandro Poli, Loredana Redaelli, Giovanna Maresca and Giovanna Petrangolini
Biomedicines 2026, 14(5), 1111; https://doi.org/10.3390/biomedicines14051111 - 14 May 2026
Viewed by 608
Abstract
Background: Metabolic syndrome is characterized by dysregulated glucose metabolism and is a major risk factor for type 2 diabetes mellitus and cardiovascular disease. Although glucose-lowering therapies such as glucagon-like peptide-1 receptor (GLP-1R) agonists are effective, their use may be limited by cost, administration [...] Read more.
Background: Metabolic syndrome is characterized by dysregulated glucose metabolism and is a major risk factor for type 2 diabetes mellitus and cardiovascular disease. Although glucose-lowering therapies such as glucagon-like peptide-1 receptor (GLP-1R) agonists are effective, their use may be limited by cost, administration route, side effects and tolerability. Bergamot (Citrus bergamia Risso et Poiteau) extract, rich in flavanones, has shown favorable metabolic effects in clinical studies, although its mechanisms of action remain insufficiently defined. This study aimed to investigate the potential glucose-modulating mechanisms of a standardized phospholipid-formulated bergamot extract (BP) (Vazguard™) in vitro. Methods: GLP-1R activation was assessed in a U2OS cell line expressing cyclic adenosine monophosphate (cAMP)-sensitive Nomad Biosensors™. Dipeptidyl peptidase-4 (DPP4) activity was evaluated using a cell-free enzymatic assay, while Glucose transporter type 4 (GLUT4)-mediated glucose uptake was assessed in CHO-K1 cells stably expressing human GLUT4 using an adenosine triphosphate (ATP)-based readout. Cytotoxicity was also using lactate dehydrogenase (LDH), MTT, and nuclei count assays. Results: BP exhibited a dose-dependent (0.31–5 mg/mL) increase in cAMP biosensor fluorescence, consistent with GLP-1R-associated signaling and a maximal response of approximately 60% relative to the positive control (GLP-1R agonist II). No cytotoxic effects were observed. In contrast, BP showed no inhibitory effect on DPP4 activity and did not alter GLUT4-mediated glucose uptake under the experimental conditions tested. Conclusions: These findings provide novel mechanistic evidence that phospholipid-formulated bergamot extract suggests a possible involvement in GLP-1R-associated signaling in vitro, without detectable effects on DPP4 or GLUT4 pathways under the conditions tested. This suggests a mechanism consistent with weak agonist or allosteric modulation of GLP-1R and supports further investigation of bergamot formulated with phospholipids as potential natural adjuncts in metabolic health management. Full article
(This article belongs to the Special Issue Cardiometabolic Diseases: Molecular Biomarkers and Treatment Strategies)
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Review

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14 pages, 1523 KB  
Review
Male Obesity and Cardiometabolic Risk: Inflammatory Mechanisms and Clinical Implications
by Rodolfo de Oliveira Medeiros, Cristiano Machado Galhardi, Carlos Horacio Vargas Urzagaste, Camila Menon Oliveros, Gustavo Silveira Pires, Vinícius Willian Calderon da Silva, Felipe Quieregati de Novaes, Isabela Gazola Suzuki, Hugo Calesso dos Reis, José Antonio Pizzolato Neto, Felipe Ravazzi Guzzo, Marcus Vinicius da Silva Zanelato, Rafael Ignácio dos Santos, Pedro Henrique Lima Domingues, Bruna Gonçalves Manzoni, Melissa Antunes, Teófilo Augusto Araújo Tiradentes, Victor Cáppia, Thiago Luengo Tavares and Altair Martins Barasuol
Biomedicines 2026, 14(7), 1414; https://doi.org/10.3390/biomedicines14071414 - 23 Jun 2026
Viewed by 275
Abstract
Obesity is a major global health challenge strongly associated with increased cardiometabolic morbidity and mortality. In men, obesity is characterized by a predominance of visceral adiposity, which is metabolically active and closely linked to systemic inflammation, hormonal dysregulation, and adverse cardiovascular outcomes. Despite [...] Read more.
Obesity is a major global health challenge strongly associated with increased cardiometabolic morbidity and mortality. In men, obesity is characterized by a predominance of visceral adiposity, which is metabolically active and closely linked to systemic inflammation, hormonal dysregulation, and adverse cardiovascular outcomes. Despite its clinical relevance, male obesity remains underrecognized as a distinct pathophysiological condition. This study aimed to analyze the inflammatory mechanisms underlying male obesity and their relationship with cardiometabolic risk. A structured narrative review was conducted based on a PICo-guided research question, with literature searches performed in PubMed/MEDLINE, Scopus, Web of Science, Embase, and ScienceDirect, covering publications from 2015 to 2026. Studies focusing on male obesity, inflammatory pathways, and cardiometabolic outcomes were included. Evidence indicates that visceral adipose tissue acts as an active endocrine organ, releasing pro-inflammatory cytokines such as TNF-α and IL-6, contributing to chronic low-grade inflammation. This inflammatory state is associated with insulin resistance (IR), endothelial dysfunction, and oxidative stress, mediated by intracellular pathways including NF-κB and JNK. Additionally, adipokine imbalance, characterized by reduced adiponectin and increased leptin levels, further exacerbates metabolic and vascular impairment. Hormonal alterations, particularly reduced testosterone levels, play a key role in amplifying visceral fat accumulation and inflammation, creating a bidirectional relationship between hypogonadism and metabolic dysfunction. Clinically, these mechanisms highlight the importance of integrating inflammatory biomarkers, body composition assessment, and hormonal evaluation into the management of male obesity. Emerging therapies, including GLP-1 receptor agonists and immunometabolic interventions, offer promising strategies for reducing cardiometabolic risk. In conclusion, male obesity represents a complex, inflammation-driven condition requiring a comprehensive and mechanism-based approach to improve clinical outcomes and guide future therapeutic developments. Full article
(This article belongs to the Special Issue Cardiometabolic Diseases: Molecular Biomarkers and Treatment Strategies)
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27 pages, 1053 KB  
Review
Gut Microbiota as an Innovative Therapeutic Target in Cardiovascular Diseases from a Metabolic and Inflammatory Perspective
by Emília Hijová, Izabela Bertková and Veronika Benetinová
Biomedicines 2026, 14(6), 1267; https://doi.org/10.3390/biomedicines14061267 - 1 Jun 2026
Viewed by 531
Abstract
The gut microbiome plays a key role in the pathogenesis of cardiovascular disease through systemic inflammation, impaired lipid metabolism, and proatherogenic gut metabolites like trimethylamine N-oxide. Gut dysbiosis contributes to decreased level of microbial metabolites such as short-chain fatty acids, bile acids, coprostanol, [...] Read more.
The gut microbiome plays a key role in the pathogenesis of cardiovascular disease through systemic inflammation, impaired lipid metabolism, and proatherogenic gut metabolites like trimethylamine N-oxide. Gut dysbiosis contributes to decreased level of microbial metabolites such as short-chain fatty acids, bile acids, coprostanol, and phenylacetylglutamine, as well as increased intestinal permeability and platelet hyper-reactivity, and exacerbating cardiovascular risk. New microbiome-focused treatments such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation are showing potential to help reduce cardiovascular diseases. However, bringing these therapies into clinical settings is difficult because they vary by strain and individual response. The gut–heart connection offers an innovative approach to preventing and treating heart condition, but additional research is needed to ensure lasting effectiveness and safety. Full article
(This article belongs to the Special Issue Cardiometabolic Diseases: Molecular Biomarkers and Treatment Strategies)
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