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Translational Medicine of Vascular and Lymphatic Diseases: From the Molecule to the Clinic

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 August 2024) | Viewed by 8236

Special Issue Editors

Dr. Miguel Ortega

E-Mail Website
Guest Editor
Department of Medicine and Medical Specialities, IRYCYS, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Interests: vascular diseases; artery; venous disease; venous hypertension; heart; lymph; diabetes; immune system; translational medicine
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Melchor Álvarez de Mon

E-Mail Website
Guest Editor
1. Department of Medicine and Medical Specialities, IRYCYS, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
2. Immune System Diseases-Rheumatology and Internal Medicine Service, University Hospital Príncipe de Asturias, (CIBEREHD), 28806 Alcala de Henares, Spain
Interests: immune system; systemic diseases; semiology; cytokines; translational medicine
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Natalio García-Honduvilla

E-Mail Website
Guest Editor
Department of Medicine and Medical Specialities, IRYCYS, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Interests: tissue engineering; vascular medicine; targeted therapies; translational medicine
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Julia Bujan

E-Mail Website
Guest Editor
Department of Medicine and Medical Specialities, IRYCYS, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Interests: artery; histology; vascular medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We present this Special Issue that aims to address vascular pathology from a translational perspective. We want this Special Issue to be a place of synergies of molecular and clinical advances in the field of vascular medicine.

Dr. Miguel Ortega
Prof. Dr. Melchor Álvarez de Mon
Prof. Dr. Natalio García-Honduvilla
Prof. Dr. Julia Bujan
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 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • vascular diseases
  • artery
  • venous disease
  • venous hypertension
  • heart
  • lymph
  • diabetes
  • immune system
  • translational medicine

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Published Papers (6 papers)

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Research

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15 pages, 564 KiB  
Article
Interleukin-6: Cardiovascular Aspects of Long-Term Cytokine Suppression in Patients with Rheumatoid Arthritis
by Elena V. Gerasimova, Tatiana V. Popkova, Irina G. Kirillova, Daria A. Gerasimova, Evgenii L. Nasonov and Aleksandr M. Lila
Int. J. Mol. Sci. 2024, 25(22), 12425; https://doi.org/10.3390/ijms252212425 - 19 Nov 2024
Viewed by 318
Abstract
In recent years, many atherogenesis researchers have focused on the role of inflammatory cytokines in the development of cardiovascular disease (CVD). Interleukin-6 (IL-6) cytokine is independently associated with higher CVD risk in patients with rheumatoid arthritis (RA). The effect of IL-6 inhibitors on [...] Read more.
In recent years, many atherogenesis researchers have focused on the role of inflammatory cytokines in the development of cardiovascular disease (CVD). Interleukin-6 (IL-6) cytokine is independently associated with higher CVD risk in patients with rheumatoid arthritis (RA). The effect of IL-6 inhibitors on the cardiovascular system in RA patients remains poorly understood, especially with its long-term use. This study investigates the effect of therapy with IL-6 receptor blocker tocilizumab (TCZ) on the dynamics of cardiovascular risk (CVR), modifiable risk factors (RFs), carotid artery (CA) structural changes, and the incidence of cardiovascular complications (CVCs) in RA patients during a 265-week follow-up period. Forty-five patients with active RA (DAS28-ESR 6.2 (5.5;6.8) with ineffectiveness and/or intolerance to disease-modifying antirheumatic drugs (DMARDs) were included in this study. During long-term therapy with TCZ in RA patients, no increase in CVR and no significant structural changes in CA were observed. No significant changes in the blood lipid spectrum were observed in patients without statin therapy. In the group of patients receiving statins, there was a 43% increase in high-density lipoprotein cholesterol (HDL-C), a 15% reduction in total cholesterol levels, and a 56% decrease in the atherogenicity index (p < 0.01 in all cases). Associations were found between ∆ total cholesterol and ∆ C-reactive protein (CRP) (R = 0.36, p = 0.04), ∆ low-density lipoprotein cholesterol (LDL-C), and ∆-CRP (R = 0.42, p = 0.03) in RA patients receiving statins. Initially, the thickness of the intima–media complex of carotid arteries (cIMT) positively moderately correlated with age (R = 0.7; p < 0.01), BMI (R = 0.37; p < 0.01), and systolic blood pressure (R = 0.64; p < 0.01); however, it weakly correlated with the lipid spectrum parameters: total cholesterol (R = 0.29; p < 0.01) and LDL-C (R = 0.33; p < 0.01). No new associations of cIMT by the end of the follow-up period, as well as the relationship of cIMT value with RA activity and therapy, were revealed. Patients with carotid ASPs showed an oppositely directed relationship between total cholesterol and sVCAM-1 at baseline (R = −0.25, p = 0.01) and at the end of this study (R = 0.29, p < 0.01). The incidence of cardiovascular events was 0.53 per 100 patient-years during the 265-week period of TCZ therapy. Full article
(This article belongs to the Special Issue Translational Medicine of Vascular and Lymphatic Diseases: From the Molecule to the Clinic)
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19 pages, 2985 KiB  
Article
Localization of Hemostasis Elements in Aspirated Coronary Thrombi at Different Stages of Evolution
by Dóra Pituk, László Balogh, Emőke Horváth, Zoltán Hegyi, Barbara Baráth, Réka Bogáti, Péter Szűcs, Zoltán Papp, Éva Katona and Zsuzsanna Bereczky
Int. J. Mol. Sci. 2024, 25(21), 11746; https://doi.org/10.3390/ijms252111746 - 1 Nov 2024
Viewed by 488
Abstract
The structure of aspirated coronary thrombus in ST-segment elevation myocardial infarction (STEMI) is still being studied. Our aims were to characterize coronary thrombi of different ages, focusing on the appearance of activated protein C (APC/PC) and its relation to the elements of neutrophil [...] Read more.
The structure of aspirated coronary thrombus in ST-segment elevation myocardial infarction (STEMI) is still being studied. Our aims were to characterize coronary thrombi of different ages, focusing on the appearance of activated protein C (APC/PC) and its relation to the elements of neutrophil extracellular traps (NETs), and the factors closely related to fibrin as factor XIII (FXIII) and α2 plasmin inhibitor (α2-PI). The thrombi of n = 24 male patients with atherosclerotic coronary plaque rupture related to native coronary artery occlusion were selected for histopathology analysis. Thrombus age was distinguished as fresh, lytic, and organized, and then analyzed by immunofluorescent staining and confocal microscopy. FXIII was present at a high level and showed a high degree of co-localization with fibrin in all stages of thrombus evolution. The amount of α2-PI was low in the fresh thrombi, which increased significantly to the lytic phase. It was evenly distributed and consistently associated with fibrin. APC/PC appeared in the fresh thrombus and remained constant during its evolution. The presence of NET marker and CD66b was most dominant in the lytic phase. APC/PC co-localization with the elements of NET formation shows its role in NET degradation. These observations suggest the importance of searching for further targeted therapeutic strategies in STEMI patients. Full article
(This article belongs to the Special Issue Translational Medicine of Vascular and Lymphatic Diseases: From the Molecule to the Clinic)
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15 pages, 2534 KiB  
Article
Exacerbated Activation of the NLRP3 Inflammasome in the Placentas from Women Who Developed Chronic Venous Disease during Pregnancy
by María Asunción Sánchez-Gil, Oscar Fraile-Martinez, Cielo García-Montero, Diego De Leon-Oliva, Diego Liviu Boaru, Patricia De Castro-Martinez, Adrían Camacho-Alcázar, Juan A. De León-Luis, Coral Bravo, Raúl Díaz-Pedrero, Laura López-Gonzalez, Julia Bujan, María J. Cancelo, Melchor Álvarez-Mon, Natalio García-Honduvilla, Miguel A. Saez and Miguel A. Ortega
Int. J. Mol. Sci. 2024, 25(10), 5528; https://doi.org/10.3390/ijms25105528 - 18 May 2024
Viewed by 1150
Abstract
Chronic venous disease (CVD) comprises a spectrum of morphofunctional disorders affecting the venous system, affecting approximately 1 in 3 women during gestation. Emerging evidence highlights diverse maternofetal implications stemming from CVD, particularly impacting the placenta. While systemic inflammation has been associated with pregnancy-related [...] Read more.
Chronic venous disease (CVD) comprises a spectrum of morphofunctional disorders affecting the venous system, affecting approximately 1 in 3 women during gestation. Emerging evidence highlights diverse maternofetal implications stemming from CVD, particularly impacting the placenta. While systemic inflammation has been associated with pregnancy-related CVD, preliminary findings suggest a potential link between this condition and exacerbated inflammation in the placental tissue. Inflammasomes are major orchestrators of immune responses and inflammation in different organs and systems. Notwithstanding the relevance of inflammasomes, specifically the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3)- which has been demonstrated in the placentas of women with different obstetric complications, the precise involvement of this component in the placentas of women with CVD remains to be explored. This study employs immunohistochemistry and real-time PCR (RT-qPCR) to examine the gene and protein expression of key components in both canonical and non-canonical pathways of the NLRP3 inflammasome (NLRP3, ASC—apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain—caspase 1, caspase 5, caspase 8, and interleukin 1β) within the placental tissue of women affected by CVD. Our findings reveal a substantial upregulation of these components in CVD-affected placentas, indicating a potential pathophysiological role of the NLRP3 inflammasome in the development of this condition. Subsequent investigations should focus on assessing translational interventions addressing this dysregulation in affected patient populations. Full article
(This article belongs to the Special Issue Translational Medicine of Vascular and Lymphatic Diseases: From the Molecule to the Clinic)
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Review

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14 pages, 1168 KiB  
Review
The Role of Muscarinic Acetylcholine Receptor M3 in Cardiovascular Diseases
by Xinxing Liu, Yi Yu, Haiying Zhang, Min Zhang and Yan Liu
Int. J. Mol. Sci. 2024, 25(14), 7560; https://doi.org/10.3390/ijms25147560 - 10 Jul 2024
Viewed by 2094
Abstract
The muscarinic acetylcholine receptor M3 (M3-mAChR) is involved in various physiological and pathological processes. Owing to specific cardioprotective effects, M3-mAChR is an ideal diagnostic and therapeutic biomarker for cardiovascular diseases (CVDs). Growing evidence has linked M3-mAChR [...] Read more.
The muscarinic acetylcholine receptor M3 (M3-mAChR) is involved in various physiological and pathological processes. Owing to specific cardioprotective effects, M3-mAChR is an ideal diagnostic and therapeutic biomarker for cardiovascular diseases (CVDs). Growing evidence has linked M3-mAChR to the development of multiple CVDs, in which it plays a role in cardiac protection such as anti-arrhythmia, anti-hypertrophy, and anti-fibrosis. This review summarizes M3-mAChR’s expression patterns, functions, and underlying mechanisms of action in CVDs, especially in ischemia/reperfusion injury, cardiac hypertrophy, and heart failure, opening up a new research direction for the treatment of CVDs. Full article
(This article belongs to the Special Issue Translational Medicine of Vascular and Lymphatic Diseases: From the Molecule to the Clinic)
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18 pages, 791 KiB  
Review
Regenerative Peripheral Nerve Interfaces (RPNIs) in Animal Models and Their Applications: A Systematic Review
by Jorge González-Prieto, Lara Cristóbal, Mario Arenillas, Romano Giannetti, José Daniel Muñoz Frías, Eduardo Alonso Rivas, Elisa Sanz Barbero, Ana Gutiérrez-Pecharromán, Francisco Díaz Montero and Andrés A. Maldonado
Int. J. Mol. Sci. 2024, 25(2), 1141; https://doi.org/10.3390/ijms25021141 - 17 Jan 2024
Cited by 1 | Viewed by 1183
Abstract
Regenerative Peripheral Nerve Interfaces (RPNIs) encompass neurotized muscle grafts employed for the purpose of amplifying peripheral nerve electrical signaling. The aim of this investigation was to undertake an analysis of the extant literature concerning animal models utilized in the context of RPNIs. A [...] Read more.
Regenerative Peripheral Nerve Interfaces (RPNIs) encompass neurotized muscle grafts employed for the purpose of amplifying peripheral nerve electrical signaling. The aim of this investigation was to undertake an analysis of the extant literature concerning animal models utilized in the context of RPNIs. A systematic review of the literature of RPNI techniques in animal models was performed in line with the PRISMA statement using the MEDLINE/PubMed and Embase databases from January 1970 to September 2023. Within the compilation of one hundred and four articles employing the RPNI technique, a subset of thirty-five were conducted using animal models across six distinct institutions. The majority (91%) of these studies were performed on murine models, while the remaining (9%) were conducted employing macaque models. The most frequently employed anatomical components in the construction of the RPNIs were the common peroneal nerve and the extensor digitorum longus (EDL) muscle. Through various histological techniques, robust neoangiogenesis and axonal regeneration were evidenced. Functionally, the RPNIs demonstrated the capability to discern, record, and amplify action potentials, a competence that exhibited commendable long-term stability. Different RPNI animal models have been replicated across different studies. Histological, neurophysiological, and functional analyses are summarized to be used in future studies. Full article
(This article belongs to the Special Issue Translational Medicine of Vascular and Lymphatic Diseases: From the Molecule to the Clinic)
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Other

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9 pages, 1929 KiB  
Case Report
An Uncommon Case of Moyamoya Syndrome Is Accompanied by an Arteriovenous Malformation with the Involvement of Dural Arteries
by Chingiz Nurimanov, Iroda Mammadinova, Yerbol Makhambetov and Serik Akshulakov
Int. J. Mol. Sci. 2023, 24(6), 5911; https://doi.org/10.3390/ijms24065911 - 21 Mar 2023
Cited by 1 | Viewed by 2305
Abstract
(1) Background: This report describes the surgical management of a case of concurrent AVM with the involvement of dural arteries and moyamoya syndrome. Given the infrequency of this combination, there is currently no established management strategy available. (2) Case Description: A 49-year-old male [...] Read more.
(1) Background: This report describes the surgical management of a case of concurrent AVM with the involvement of dural arteries and moyamoya syndrome. Given the infrequency of this combination, there is currently no established management strategy available. (2) Case Description: A 49-year-old male patient with multiple symptoms including headaches, tinnitus, and visual impairment diagnosed with the coexistence of an arteriovenous malformation with the involvement of dural arteries and moyamoya syndrome was admitted to the national tertiary hospital. The patient underwent surgical management through embolization of the AVM from the afferents of the dural arteries, which has resulted in positive clinical outcomes. However, this approach may not be suitable for all cases, and a multidisciplinary team approach may be required to develop an individualized treatment strategy. (3) Conclusion: The contradictory nature of the treatment approaches in cases of combined AVM with the involvement of dural arteries and MMD highlights the complex nature of this condition and the need for further research to identify the most effective treatment strategies. Full article
(This article belongs to the Special Issue Translational Medicine of Vascular and Lymphatic Diseases: From the Molecule to the Clinic)
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