Submit to Special Issue Submit Abstract to Special Issue Review for Biomedicines Propose a Special Issue

Journal Menu

Journal Browser

Animal Models for the Study of Cardiovascular Physiology—Second Edition

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Related Special Issue
Published Papers

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 31 August 2026 | Viewed by 10411

Share This Special Issue

Special Issue Editor

Dr. Sandra Lia Amaral

E-Mail Website
Guest Editor

1. Department of Physical Education, São Paulo State University-UNESP, Campus of Bauru, Bauru, SP, Brazil
2. Joint Graduate Program in Physiological Sciences (PIPGCF), Federal University of Sao Carlos and São Paulo State University, UFSCar/UNESP, São Carlos, Brazil
Interests: hypertension; skeletal muscle; arterial stiffness; exercise training
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cardiovascular diseases, which include coronary heart disease, cerebrovascular disease, rheumatic heart disease, peripheral vascular disease, and other conditions, represent the leading cause of death worldwide. Stroke and ischemic diseases are among the top 10 diseases regarding mortality rate worldwide, and these conditions are also consequences of hypertension. Since there are several behavioral risk factors for cardiovascular diseases, such as an unhealthy diet, physical inactivity, tobacco consumption, and the harmful use of alcohol, associated with hypertension, diabetes, and excess weight, the treatment for these pathologies can be very complex. Therefore, a deeper understanding of the disease mechanisms of cardiovascular diseases could significantly contribute to more effective treatment and to a reduction in premature deaths from these diseases. Animal models are useful as they represent the main strategy for exploring the different mechanisms involved in cardiovascular diseases. Overall, this Special Issue invites you and your colleagues to share your expertise and knowledge by submitting original research articles, systematic reviews, and review articles that report new ideas and recent advances related to this topic.

Dr. Sandra Lia Amaral
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. 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

hypertension
stroke
myocardium infarction
arterial stiffness
supravalvular aortic stenosis
cardiac remodeling
capillary angiogenesis
exercise training
vascular diseases
non-pharmacological treatment

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Related Special Issue

Animal Models for the Study of Cardiovascular Physiology in Biomedicines (13 articles)

Published Papers (8 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

11 pages, 648 KB

Open AccessArticle

Angiotensin II Disrupts Axo-Axonal Interaction-Mediated Vasorelaxation in Basilar Arteries of Normotensive and Hypertensive Rats

by Stephen Shei-Dei Yang, Kuan-Yu Chen, Earl Fu, Hsi-Hsien Chang and Kuo-Feng Huang

Biomedicines 2026, 14(4), 853; https://doi.org/10.3390/biomedicines14040853 - 8 Apr 2026

Viewed by 567

Abstract

Background/Objectives: The renin–angiotensin–aldosterone (RAA) system is a key regulator of cardiovascular homeostasis. Recent evidence suggests that Angiotensin II (Ang II) can trigger ferroptosis, an iron-dependent form of cell death. We previously demonstrated that periodontitis induces neurovascular dysfunction, and our preliminary observations indicate that this oral inflammatory model is associated with elevated blood pressure. However, the mechanism by which Ang II impaired nitrergic vasodilation and triggered ferroptosis in cerebral arteries remains unclear. This study investigates the functional effects of electrical and chemical nerve stimulation in adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Methods: Endothelium-denuded basilar arterial (BA) rings from SHRs and WKYs were used to assess the impact of Ang II on neurogenic relaxation via wire myography. Results: Vascular relaxation responses to nicotine and transmural nerve stimulation (TNS) were significantly diminished in SHRs compared to WKYs. This impairment was reversed by both acute preincubation and chronic treatment with losartan (an AT1 receptor antagonist). In WKY BAs, exogenous Ang II pretreatment inhibited relaxation responses to nicotine, TNS, and isoproterenol. Importantly, this inhibition was effectively reversed by marimastat (MMP inhibitor), catalase (antioxidant), and ferrostatin-1 (ferroptosis inhibitor). Conclusions: Our findings indicate that Ang II induces functional alterations in neurovascular signaling patterns by triggering ferroptosis within nerve terminals. This process leads to a functional imbalance between sympathetic and parasympathetic influences, ultimately impairing neurogenic nitrergic dilation in the BAs of SHRs. These results suggest that targeting Ang II-induced ferroptosis may alleviate the neuroinflammation and cognitive decline associated with hypertension-related cerebrovascular dysfunction. Full article

(This article belongs to the Special Issue Animal Models for the Study of Cardiovascular Physiology—Second Edition)

► Show Figures

Figure 1

14 pages, 2413 KB

Open AccessArticle

Involvement of Secondary Induced Thrombus on Hemorrhage Induced by Both Delayed Recanalization and Delayed t-PA Treatment in Murine Ischemic Stroke Models

by Yuhki Moriike, Yumeta Nakano, Yasuki Matano, Yasuhiro Suzuki, Kazuo Umemura and Nobuo Nagai

Biomedicines 2026, 14(2), 308; https://doi.org/10.3390/biomedicines14020308 - 29 Jan 2026

Viewed by 588

Abstract

Background: In the treatment of ischemic stroke, both tissue-type plasminogen activator (t-PA) thrombolytic and endovascular therapy are employed; however, delayed intervention with these therapies increases the risk of hemorrhage. Hemorrhage associated with delayed t-PA treatment involves the activation of plasmin and matrix metalloproteinases (MMPs); however, the detailed mechanisms underlying I/R activation remain unclear. Objectives: This study examined the effects of delayed recanalization on ischemic stroke in a permanent middle cerebral artery (MCA) occlusion (MCA-O) model, and a novel MCA ischemia/reperfusion (I/R) model: 2-h ischemia followed by reperfusion (I/R 2 h), and 4.5-h ischemia followed by reperfusion (I/R 4.5 h). Secondary induced thrombus (SIT) formation, hemorrhage, MMP activity, MMP-9 immunoreactivity, and tomato lectin (TL) staining, as well as the effects of t-PA and heparin treatment were evaluated. Results: SIT formed within 1 h after reperfusion in the I/R 4.5 h model only, while t-PA or heparin treatment reduced SIT formation. Hemorrhage increased with or without t-PA administration in the I/R 4.5 h model, but it was suppressed by heparin pretreatment. MMP activity and MMP-9 immunoreactivity were localized to the SIT. Additionally, a negative staining area for TL was observed in the damaged area, where SIT formed in the I/R 4.5 h model. Conclusions: These results suggest that delayed recanalization induces SIT via glycocalyx degradation, leading to hemorrhage via plasmin/MMP-9 activation by endogenous and exogenous t-PA-mediated fibrinolysis in novel murine models of ischemic stroke. Furthermore, inhibition of SIT formation is beneficial for suppressing hemorrhages associated with delayed recanalization after endovascular or t-PA therapy. Full article

(This article belongs to the Special Issue Animal Models for the Study of Cardiovascular Physiology—Second Edition)

► Show Figures

Graphical abstract

16 pages, 1249 KB

Open AccessArticle

Rosmarinic Acid Induces Vasorelaxation via Endothelium-Dependent, Potassium Channel-Related, and Calcium-Modulated Pathways: Evidence from Rat Aortic Rings

by Serdar Sahinturk and Naciye Isbil

Biomedicines 2025, 13(12), 2936; https://doi.org/10.3390/biomedicines13122936 - 29 Nov 2025

Cited by 1 | Viewed by 1153

Abstract

Background: Hypertension and its complications are a major global health problem, and natural compounds with vasorelaxant effects are being investigated as potential antihypertensive agents. Objective: This study aimed to determine whether rosmarinic acid (RA) induces vasorelaxation in the rat thoracic aorta and to elucidate the underlying mechanisms. Methods: Isolated thoracic aortic rings, with or without endothelium, were precontracted with phenylephrine and subsequently exposed to cumulative concentrations of RA. The roles of endothelium-derived factors, potassium channels, and calcium signaling were evaluated using selective pharmacological inhibitors and activators. In addition, the involvement of the AMPK pathway, adenylate cyclase/cAMP pathway, PKC signaling, β-adrenergic receptors, muscarinic receptors, and angiotensin II in RA-induced vasorelaxation was investigated. Results: RA induced a concentration-dependent vasorelaxation in endothelium-intact thoracic aortic rings (p < 0.001; pD₂ = 7.67 ± 0.04). The vasorelaxant effect of RA was attenuated in endothelium-denuded vessels (pD2: 5.26 ± 0.18). The relaxation response was significantly attenuated by inhibitors of the PI3K/Akt/eNOS/NO/cGMP pathway and by blockers of BK_Ca, IK_Ca, and Kv potassium channels (p < 0.001). Furthermore, RA markedly inhibited both extracellular Ca²⁺ influx and intracellular Ca²⁺ release from the sarcoplasmic reticulum (p < 0.001). RA incubation also significantly reduced the contractions induced by angiotensin II (Ang II) and by the PKC activator PMA (p < 0.001). Other tested pathways had no significant influence on the vasorelaxant effect of RA (p > 0.05). Conclusions: These findings demonstrate that rosmarinic acid induces both endothelium-dependent and endothelium-independent vasorelaxation in the rat thoracic aorta through activation of the PI3K/Akt/eNOS/NO/cGMP pathway, opening of BK_Ca, IK_Ca, and Kv potassium channels, and suppression of Ca²⁺ mobilization. Additionally, inhibition of PKC- and angiotensin II-mediated vascular contraction contributes to RA-induced vasorelaxation. RA may therefore have therapeutic potential in the management of hypertension. Full article

(This article belongs to the Special Issue Animal Models for the Study of Cardiovascular Physiology—Second Edition)

► Show Figures

Graphical abstract

15 pages, 7582 KB

Open AccessArticle

Novel Murine Model of Atherosclerosis Progression Induced by a Modified Paigen Diet

by María del Rosario Álvarez-Valadez, Alejandrina Rodríguez-Hernández, Felipa Andrade-Urzúa, Saraí Limón-Miranda, Adriana Ceballos-Gutiérrez, Jorge Agustín Velasco-Gutiérrez, Armando Gamboa-Domínguez, Adolfo Virgen-Ortiz and Enrique Sánchez-Pastor

Biomedicines 2025, 13(11), 2736; https://doi.org/10.3390/biomedicines13112736 - 8 Nov 2025

Cited by 1 | Viewed by 1015

Abstract

Background/Objectives: To better understand the mechanisms involved in atherosclerosis, different models have been developed, but these fail when studying the progression of this disease. The purpose of this study was to standardize a new model of atherosclerosis progression in rats using Paigen-type modified atherogenic diet. Methods: The design included a control group (n = 16) and 64 rats with atherogenic Paigen-type diet subdivided into four subgroups with different doses (Athero 1, Athero 2, Athero 3, and Athero 4). The atherogenic diet was supplemented orally in sequential stages: 1) Hypervitaminic (1.5 mL/kg/day for 12 days) and 2) Hyperlipidic (48 days ad libitum). Blood pressure, heart rate, aortic histopathology, inflammatory biomarkers, and biochemical lipid and liver profiles were measured in all groups on days 30 and 60. Results: All Athero 1 rats were sacrificed due to a poisoning for vitamin D2 excess. Athero 2 rats were sacrificed at day 30 showing severe atherosclerotic lesions (grades V–VIII). Athero 3 rats showed mild lesions (I–IV) at day 30 and severe lesions (V–VIII) at day 60. Athero 4 rats showed mild lesions (I–IV) at days 30 and 60. Diet-dependent changes in blood pressure and heart rate were observed. Furthermore, glycemia, dyslipidemia, and liver profile were associated with the degree of atherosclerotic lesion. Conclusions: “Athero 3” atherogenic diet generates a stable model to study the progress of atherosclerosis in rats. Full article

(This article belongs to the Special Issue Animal Models for the Study of Cardiovascular Physiology—Second Edition)

► Show Figures

Graphical abstract

Review

Jump to: Research

21 pages, 3031 KB

Open AccessReview

Zebrafish as a Model for Cardiovascular Disease Using Nanotechnology and Emerging Optogenetic Tools

by Phuc Nguyen, Vanessa Avila and Juhyun Lee

Biomedicines 2026, 14(3), 596; https://doi.org/10.3390/biomedicines14030596 - 7 Mar 2026

Viewed by 750

Abstract

Recent advances in experimental model systems have improved our ability to study cardiovascular development, function, and disease with high spatial and temporal resolution. The zebrafish (Danio rerio) has emerged as a powerful vertebrate model for cardiovascular research due to its transparency, genetic tractability, and conserved cardiac physiology, similar to humans. These features allow real-time in vivo imaging, the functional assessment of cardiac performance, and the tracking of signaling pathways that are fundamental in cardiovascular development and disease. Recent advances in nanotechnology and optogenetics have introduced complementary tools for probing and manipulating cardiovascular systems with high spatial and temporal precision. Nanoparticle-based platforms enable the tunable delivery of drugs, nucleic acids, and imaging agents, while optogenetic systems allow the light-mediated control of gene expression, signaling pathways, and cardiac electrophysiology. In this review, we summarize recent progress in the application of nanoparticle-based technologies and the emerging optogenetic tools in zebrafish cardiovascular research, including the optical control of cardiac signaling and electrophysiology. We briefly discuss emerging complementary efforts toward nanoparticle and optogenetic approaches, how to overcome key technical limitations, such as light penetration and gene delivery, and how to facilitate the development of fully optical platforms for cardiovascular disease modeling and drug screening. Full article

(This article belongs to the Special Issue Animal Models for the Study of Cardiovascular Physiology—Second Edition)

► Show Figures

Figure 1

17 pages, 883 KB

Open AccessReview

Animal Models of Aortic Aneurysm and Dissection: A Comparative Guide for Mechanism, Therapeutic Testing, and Translational Readouts

by Shayan Mohammadmoradi and Sidney W. Whiteheart

Biomedicines 2026, 14(1), 170; https://doi.org/10.3390/biomedicines14010170 - 13 Jan 2026

Viewed by 1167

Abstract

Aortic aneurysms and dissections are devastating vascular diseases with high mortality, yet no pharmacological therapy has proven effective in halting growth or preventing rupture. Surgical and endovascular repair remain the only treatment options for advanced disease. Animal models have been indispensable in defining mechanisms and testing candidate therapies, but the diversity of protocols, strain-dependent variability, and heterogeneous endpoints complicate interpretation and translation. This review provides an update focused on how to match models to specific research questions. We critically compare commonly used abdominal aortic aneurysm (AAA) models (angiotensin II ± hyperlipidemia, elastase, calcium chloride, β-aminopropionitrile BAPN hybrids, and mineralocorticoid agonist/fludrocortisone models) with thoracic aortopathy and dissection models (BAPN alone or with AngII, genetic models including Marfan and smooth muscle contractile mutations, and AngII + TGF-β blockade). We highlight practical considerations on segment specificity, rupture incidence, lipid dependence, comorbidities, and outcome measurement, with emphasis on rigor and reporting standards. A translational thread on platelet–intraluminal thrombus biology, including the emerging biomarker and therapeutic targets such as glycoprotein VI (GPVI), is integrated across models. We offer a decision grid and rigor checklist to harmonize model use, enhance reproducibility, and accelerate translation. Full article

(This article belongs to the Special Issue Animal Models for the Study of Cardiovascular Physiology—Second Edition)

► Show Figures

Figure 1

19 pages, 1038 KB

Open AccessReview

The Current State of Mock Circulatory Loop Applications in Aortic and Cardiovascular Research: A Scoping Review

by Felix E. N. Osinga, Nesar A. Hasami, Jasper F. de Kort, Emma-Lena Maris, Maurizio Domanin, Martina Schembri, Alessandro Caimi, Michele Conti, Constantijn E. V. B. Hazenberg, Ferdinando Auricchio, Jorg L. de Bruin, Joost A. van Herwaarden and Santi Trimarchi

Biomedicines 2026, 14(1), 28; https://doi.org/10.3390/biomedicines14010028 - 22 Dec 2025

Viewed by 1175

Abstract

Background: Mock circulatory loops (MCLs) are benchtop experimental platforms that reproduce key features of the human cardiovascular system, providing a safe, controlled, and reproducible environment for haemodynamic investigation. This scoping review aims to systematically map the current landscape of MCLs used for aortic simulation and identify major areas of application. Methods: A systematic search of PubMed, Scopus, and Web of Science identified original studies employing MCLs for aortic simulation. Eligible studies were categorized into predefined themes: (I) (bio)mechanical aortic characterization, (II) hemodynamics, (III) device testing, (IV) diagnostics, and (V) training. Data on MCL configurations, aortic models, and study objectives were synthesized narratively. Results: Eighty-four studies met the inclusion criteria. Twenty-five investigated aortic biomechanics, 23 hemodynamics, 22 device or product testing, 13 validated diagnostic imaging techniques, and one training application. Models included porcine (n = 22), human cadaveric (n = 7), canine (n = 1), ovine (n = 1), bovine (n = 1), and 3D-printed or molded aortic phantoms (n = 55). MCLs were employed to study parameters such as aortic stiffness, flow dynamics, dissection propagation, endoleaks, imaging accuracy, and device performance. Conclusions: This review provides a comprehensive overview of MCL applications in aortic research. MCLs represent a versatile pre-clinical platform for studying aortic pathophysiology and testing endovascular therapies under controlled conditions. Standardized reporting frameworks are now required to improve reproducibility and accelerate translation to patient-specific planning. Full article

(This article belongs to the Special Issue Animal Models for the Study of Cardiovascular Physiology—Second Edition)

► Show Figures

Figure 1

25 pages, 4280 KB

Open AccessReview

Deciphering the Enigma of Calcific Aortic Valve Disease: The Pivotal Role of Animal Models in Unraveling Pathogenesis and Advancing Therapeutic Strategies

by Pengning Fan, Yuqi Liu, Xingyu Qian, Fuqiang Tong, Yidan Zheng, Zhengfeng Fan, Ming Chen, Zhe Chen, Haoyang Zhai, Teng Zeng, Nianguo Dong, Fei Li, Xucong Shi and Li Xu

Biomedicines 2025, 13(10), 2369; https://doi.org/10.3390/biomedicines13102369 - 27 Sep 2025

Cited by 2 | Viewed by 3205

Abstract

Calcific aortic valve disease (CAVD) is a prevalent cardiovascular condition and is the most common heart valve disease globally. Hyperlipidemia and aging are key risk factors; consequently, with the aging global population, CAVD incidence continues to rise. Despite extensive research, the pathogenesis of CAVD remains unclear, leading to a lack of effective pharmacological therapies. Consequently, valve replacement surgery persists as the primary treatment option. Establishing suitable animal models is crucial for investigating the complex pathophysiological mechanisms of CAVD in vivo, although an optimal model has yet to be identified. This review provides a concise overview of CAVD pathogenesis and summarizes the application of common animal models—including mice, rats, rabbits, and pigs—in studying valve calcification. We specifically detail the construction of various models and their associated calcific aortic valve phenotypes. Furthermore, we outline common detection methods for assessing aortic valve calcification in these models and suggest future directions for developing improved animal models relevant to CAVD research. Full article

(This article belongs to the Special Issue Animal Models for the Study of Cardiovascular Physiology—Second Edition)

► Show Figures

Journal Menu

Journal Browser

Animal Models for the Study of Cardiovascular Physiology—Second Edition

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Related Special Issue

Published Papers (8 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI