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Cardiovascular and Metabolic Pharmacology

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

Deadline for manuscript submissions: closed (28 February 2026) | Viewed by 2972

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Guest Editor
1. Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
2. Interdepartmental Research Centre "Nutraceuticals and Food for Health (NUTRAFOOD)", University of Pisa, 56126 Pisa, Italy
3. Interdepartmental Research Centre of "Ageing Biology and Pathology", University of Pisa, 56126 Pisa, Italy
Interests: cardiovascular pharmacology; gasotransmitters; nutraceuticals; hydrogen sulfide; Brassicaceae; isothiocyanates; vascular inflammation; aging; endothelial dysfunction; hypertension; H2S-donors
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Special Issue Information

Dear Colleagues,

Despite their broad pharmacological platform, cardiovascular and metabolic diseases remain the leading causes of morbidity and mortality worldwide. Curative therapies for these conditions remain inadequate to meet medical needs, likely due to their complex pathophysiology involving closely interconnected molecular mechanisms. This Special Issue brings together original research and comprehensive reviews exploring the molecular basis of cardiovascular and metabolic diseases, including hypertension, atherosclerosis, heart failure, diabetes, hyperlipidemias and obesity. Emphasis is placed on novel drug targets, such as noncoding RNAs, ion channels, metabolic enzymes, and inflammatory mediators, as well as emerging therapeutic strategies involving gene editing, small molecules, and biologics. By focusing on molecular mechanisms, this Special Issue bridges the gap between basic science and clinical application. We also emphasize the importance of systems biology and multi-omics approaches in unraveling the complexity of diseases and the variability in drug response. Recent advances in molecular pharmacology have shed new light on the signaling pathways, genetic regulators, and metabolic networks underlying disease development and progression. This Special Issue also uncovers novel molecular mechanisms that could potentially advance the prevention and management of cardiovascular and metabolic diseases in the era of personalized medicine.

Dr. Alma Martelli
Guest Editor

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Keywords

  • cardiovascular pharmacology
  • metabolic pharmacology
  • hypertension
  • diabetes
  • obesity
  • atherosclerosis
  • hyperlipidemias
  • heart failure

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Published Papers (2 papers)

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Research

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13 pages, 2215 KB  
Article
GPR18 Deletion in Mice Inversely Affects Vasoactive Signaling and Passive Biomechanical Properties of the Thoracic Aorta and Femoral Artery
by Sofie De Moudt, Ameziane Herzine, Marc-Damien Lourenco Rodrigues, Maud Collin, Magnus Bäck, Frances T. Yen and Nathalie Mercier
Int. J. Mol. Sci. 2026, 27(2), 841; https://doi.org/10.3390/ijms27020841 - 14 Jan 2026
Viewed by 402
Abstract
The G protein-coupled receptor GPR18, engaged by pro-resolving and cannabinoid-related lipid ligands, plays a vascular bed-specific protective role in endothelial function. The aim of the present study was to establish the vasoreactivity and passive biomechanical properties of the thoracic aorta and femoral artery [...] Read more.
The G protein-coupled receptor GPR18, engaged by pro-resolving and cannabinoid-related lipid ligands, plays a vascular bed-specific protective role in endothelial function. The aim of the present study was to establish the vasoreactivity and passive biomechanical properties of the thoracic aorta and femoral artery of adult GPR18 knockout compared with wildtype mice, using ex vivo myography, arterial morphology, and immunohistochemistry. The results revealed heightened receptor-independent contractility, loss of prostanoid-dependent contractile responses, altered vascular smooth muscle cell (VSMC) calcium handling, and an attenuated stress–tension relationship in the thoracic aorta of GPR18 knockout mice. This phenotype was almost entirely reversed in the femoral artery, with attenuated receptor-independent contractility, unchanged VSMC calcium handling, and a heightened stress–tension relationship in GPR18 knockout mice. These vascular bed-specific differences highlight the need to consider tissue context in the development of GPR18-based vasculoprotective therapies for cardiovascular disease. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Pharmacology)
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Review

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26 pages, 2644 KB  
Review
Interplay Between KLF4, STAT, IRF, and NF-κB in VSMC and Macrophage Plasticity During Vascular Inflammation and Atherosclerosis
by Natalia Lopacinska, Joanna Wesoly and Hans A. R. Bluyssen
Int. J. Mol. Sci. 2025, 26(20), 10205; https://doi.org/10.3390/ijms262010205 - 20 Oct 2025
Cited by 2 | Viewed by 2310
Abstract
Atherosclerosis is characterized by atherosclerotic plaque formation in large and medium vessels, mediated by endothelial cell (EC) dysfunction, altered contractility of Vascular Smooth Muscle Cells (VSMCs) and recruitment of blood leukocytes to the injured vascular endothelium. These include macrophages (MØ), T lymphocytes, and [...] Read more.
Atherosclerosis is characterized by atherosclerotic plaque formation in large and medium vessels, mediated by endothelial cell (EC) dysfunction, altered contractility of Vascular Smooth Muscle Cells (VSMCs) and recruitment of blood leukocytes to the injured vascular endothelium. These include macrophages (MØ), T lymphocytes, and dendritic cells, which drive the production of many inflammatory mediators and the process of chronic inflammation. Also, de-differentiation or phenotypic switching of VSMCs contributes to vascular remodeling and the pathogenesis of atherosclerosis. Likewise, MØ plasticity and the presence of different phenotypes have a major effect on atherosclerotic plaque formation. The multi-functional transcriptional regulator and pluripotency factor Krüppel-like factor 4 (KLF4) acts as a gatekeeper of VSMC phenotypic switching and MØ polarization during vascular inflammation and atherosclerosis. Similarly, pro-inflammatory pathways activated by Toll-like receptor (TLR)4 and Interferon gamma (IFNγ) emerge as key components of VSMC and MØ plasticity, tightly regulated by Signal Transducer and Activator of Transcription (STAT)s, Interferon Regulatory Factor (IRF)s, and Nuclear factor-κB (NF-κB). Recent discoveries predict a collaborative role of these transcription factors in different transcriptional mechanisms connected to inflammation and atherosclerosis. This review provides novel insight into the transcriptional regulatory interplay between KLF4, STATs, IRFs, and NF-κB in VSMC phenotypic switching and MØ polarization during atherogenesis. Detailed understanding of these transcriptional networks will enable us to develop novel diagnostic and therapeutic strategies to combat vascular proliferative diseases, including atherosclerosis. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Pharmacology)
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