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Cardiovascular Diseases: Histopathological and Molecular Diagnostics

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: 20 July 2025 | Viewed by 9376

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Guest Editor
Department of Morphopathology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 38 Gheorghe Marinescu Street, 540142 Targu Mures, Romania
Interests: cancer biology; GI cancer; molecular biology of cancer
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Special Issue Information

Dear Colleagues,

This Special Issue aims to present a collection of manuscripts referring to the approach to cardiovascular disorders, focusing on histological, biochemical and molecular research. We intend to realize a transdisciplinary issue and to prove that the new era in cardiology open gates for pathologists and molecular specialists. Original research, extremely rare cases with extensive review of the literature and review-type papers which are focused on cardiovascular pathology and pathophysiology, from experimental to clinical studies, are welcome. If the authors used in silico analysis or public gene databases in their manuscripts, external validation is mandatory. Your individual contribution might be useful for a new perspective on cardiovascular diseases, based on data obtained after performing in vivo or in vitro experiments, or histological, immunohistochemical and other examinations performed in clinical practice.

Prof. Dr. Simona Gurzu
Guest Editor

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Published Papers (7 papers)

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Research

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12 pages, 2619 KiB  
Article
Effects of Left Ventricular Unloading on Cardiac Function, Heart Failure Markers, and Autophagy in Rat Hearts with Acute Myocardial Infarction
by Ryota Azuma, Yasushige Shingu, Jingwen Gao and Satoru Wakasa
Int. J. Mol. Sci. 2025, 26(9), 4422; https://doi.org/10.3390/ijms26094422 - 6 May 2025
Viewed by 468
Abstract
Percutaneous ventricular assist devices are utilized in cases of cardiogenic shock following acute myocardial infarction (AMI). However, the mechanism underlying the beneficial effects of LV unloading in AMI remains unclear. This study aimed to examine the impact of LV unloading on cardiac function, [...] Read more.
Percutaneous ventricular assist devices are utilized in cases of cardiogenic shock following acute myocardial infarction (AMI). However, the mechanism underlying the beneficial effects of LV unloading in AMI remains unclear. This study aimed to examine the impact of LV unloading on cardiac function, heart failure markers, and protein degradation (autophagy and ubiquitin–proteasome system: UPS) post AMI in rats. Nine-week-old male Lewis rats were randomized into non-AMI, AMI, non-AMI with LV unloading, and AMI with LV unloading groups. LV unloading was achieved through heterotopic heart–lung transplantation. Rats were euthanized 2 and 14 days after the procedure. Cardiac functional assessment was performed using Langendorff heart perfusion. RT-PCR and Western blot analyses were conducted using the LV myocardium. The rate pressure product was comparable between the non-AMI with LV unloading group and the AMI with LV unloading at 14 days. The atrial natriuretic factor tended to be suppressed by LV unloading. LV unloading had reducing effects on the expressions of p62, selectively degraded during autophagy, both 2 and 14 days after AMI. There was no effect on the parameters for the UPS. LV unloading has a mitigating effect on the deterioration of cardiac function following AMI. Autophagy, which was suppressed by AMI, was ameliorated by LV unloading. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Histopathological and Molecular Diagnostics)
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13 pages, 4891 KiB  
Article
Histopathological Gap in Aortic Diseases: A Prospective Analysis
by Cosmin Marian Banceu, Simona Gurzu, Catalin-Bogdan Satala, Dana Ghiga, Mihai Halic Neamtu, Vladimir Voth, Markus Liebrich and Horatiu Suciu
Int. J. Mol. Sci. 2023, 24(20), 15470; https://doi.org/10.3390/ijms242015470 - 23 Oct 2023
Cited by 5 | Viewed by 1647
Abstract
Aortic dissection (AD) is a critical cardiovascular condition with the potential for devastating consequences. This study evaluated the histological changes in the aorta wall in patients with AD and aortic aneurysm (AA) who received surgical aortic replacement. Histopathological data showed that modifications of [...] Read more.
Aortic dissection (AD) is a critical cardiovascular condition with the potential for devastating consequences. This study evaluated the histological changes in the aorta wall in patients with AD and aortic aneurysm (AA) who received surgical aortic replacement. Histopathological data showed that modifications of the media layer (p = 0.0197), myxomatous aspect (p = 0.0001), and subendothelial layer degeneration (p = 0.0107) were more frequently seen in AA versus AD samples. Patients with AA were approximately twice as likely to develop histological changes than those with AD (p = 0.0037). Patients with moderate or severe medial degeneration had a higher chance of developing AD (p = 0.0001). Because the histopathological score proved to be a predictor of both in-hospital and overall mortality, its evaluation should become the standard of care in any patients who undergo aortic replacement. Individualized postoperative management might be influenced by the histopathological aspect of the aortic layer. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Histopathological and Molecular Diagnostics)
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13 pages, 990 KiB  
Communication
Remodeling of Cardiomyocytes: Study of Morphological Cellular Changes Preceding Symptomatic Ischemic Heart Failure
by Milda Kuprytė, Vaiva Lesauskaitė, Vytenis Keturakis, Vitalija Bunevičienė, Lina Utkienė, Lina Jusienė and Dalia Pangonytė
Int. J. Mol. Sci. 2023, 24(19), 14557; https://doi.org/10.3390/ijms241914557 - 26 Sep 2023
Cited by 6 | Viewed by 2122
Abstract
Although major pathogenesis mechanisms of heart failure (HF) are well established, the significance of early (mal)adaptive structural changes of cardiomyocytes preceding symptomatic ischemic HF remains ambiguous. The aim of this study is to present the morphological characterization of changes in cardiomyocytes and their [...] Read more.
Although major pathogenesis mechanisms of heart failure (HF) are well established, the significance of early (mal)adaptive structural changes of cardiomyocytes preceding symptomatic ischemic HF remains ambiguous. The aim of this study is to present the morphological characterization of changes in cardiomyocytes and their reorganization of intermediate filaments during remodeling preceding symptomatic ischemic HF in an adult human heart. A total of 84 myocardial tissue samples from middle-left heart ventricular segments were analyzed histomorphometrically and immunohistochemically, observing the cardiomyocyte’s size, shape, and desmin expression changes in the remodeling process: Stage A of HF, Stage B of HF, and Stages C/D of HF groups (ACC/AHA classification). Values p < 0.05 were considered significant. The cellular length, diameter, and volume of Stage A of HF increased predominantly by the diameter vs. the control group (p < 0.001) and continued to increase in Stage B of HF in a similar pattern (p < 0.001), increasing even more in the C/D Stages of HF predominantly by length (p < 0.001). Desmin expression was increased in Stage A of HF vs. the control group (p < 0.001), whereas it was similar in Stages A and B of HF (p > 0.05), and most intense in Stages C/D of HF (p < 0.001). Significant morphological changes of cardiomyocytes and their cytoskeletal reorganization were observed during the earliest remodeling events preceding symptomatic ischemic HF. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Histopathological and Molecular Diagnostics)
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Review

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20 pages, 1313 KiB  
Review
Ketone Bodies in the Regulation of Myocardial Perfusion in Cardiovascular Disease: Metabolic and Vasodilatory Effects
by Afolasayo A. Aromiwura, Kara R. Gouwens, Daniel C. Nguyen, Maryta Sztukowska, Luanne Didelot and Dinesh K. Kalra
Int. J. Mol. Sci. 2025, 26(10), 4856; https://doi.org/10.3390/ijms26104856 - 19 May 2025
Viewed by 356
Abstract
Ketone bodies (KBs) serve as an alternative energy source for healthy and failing hearts and have important effects on myocardial blood perfusion in both physiological and pathological states. Early animal studies suggest that KBs may provide protective benefits in ischemic heart disease and [...] Read more.
Ketone bodies (KBs) serve as an alternative energy source for healthy and failing hearts and have important effects on myocardial blood perfusion in both physiological and pathological states. Early animal studies suggest that KBs may provide protective benefits in ischemic heart disease and heart failure. Under normal circumstances, coronary blood flow regulation is an intricate system with contributions from metabolic, autonomic, compressive, and endothelial factors, with the metabolic regulatory pathway being the most significant contributor. We conducted a non-systematic review of studies published between 1987 and 2024. In this review, we explored the physiological autoregulation of normal coronary blood flow, the role of ketone bodies in myocardial perfusion in health and disease, and the potential role of exogenous ketone body supplementation in producing salutary effects on myocardial blood flow (MBF) and metabolism in exercise and cardiac disease states including ischemia, heart failure, and the aging heart. Overall, our findings demonstrated that KBs improve MBF and ejection fraction in healthy human subjects and have beneficial effects on cardiac output and left heart filling pressures in patients with decompensated heart failure. Although resting myocardial blood flow decreases with age, further studies are required to assess the impact of KBs on MBF in aging populations. Additionally, more research is needed to investigate the effects of KBs during exercise and in instances of myocardial ischemia. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Histopathological and Molecular Diagnostics)
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22 pages, 2042 KiB  
Review
High Concentrations of Circulating 2PY and 4PY—Potential Risk Factor of Cardiovascular Disease in Patients with Chronic Kidney Disease
by Agnieszka Dettlaff-Pokora and Julian Swierczynski
Int. J. Mol. Sci. 2025, 26(9), 4463; https://doi.org/10.3390/ijms26094463 - 7 May 2025
Viewed by 542
Abstract
Recently published data indicate that elevated circulating concentrations of N1-methyl-2-pyridone-5-carboxamide (2PY, also described as Met2PY) and N1-methyl-4-pyridone-5-carboxamide (4PY, also described as Met4PY), terminal catabolites of nicotinamide adenine dinucleotide (NAD+), are associated with cardiovascular disease (CVD) risk in humans. Previously, we and [...] Read more.
Recently published data indicate that elevated circulating concentrations of N1-methyl-2-pyridone-5-carboxamide (2PY, also described as Met2PY) and N1-methyl-4-pyridone-5-carboxamide (4PY, also described as Met4PY), terminal catabolites of nicotinamide adenine dinucleotide (NAD+), are associated with cardiovascular disease (CVD) risk in humans. Previously, we and the others have shown that patients with advanced stages of chronic kidney disease (CKD) exhibit several-fold higher circulating 2PY and 4PY concentrations compared to healthy subjects or patients in the early stages of the disease. It is also well documented that patients with advanced CKD stages exhibit markedly elevated CVD risk, which is the main cause of premature death (in these patients). Therefore, we hypothesize that high concentrations of circulating 2PY and 4PY are important factors that may contribute to cardiovascular events and, ultimately, premature death in CKD patients. However, further, accurately controlled clinical research is needed to provide definitive answers concerning the role of 2PY and 4PY in CVD risk in CKD patients. Moreover, we are dealing with some issues related to the use of NAD+ precursors (NAD+ boosters) as drugs (also in CKD patients) and/or supplements. Due to the increase in circulating 2PY and 4PY levels during treatment with NAD+ boosters, these precursors should be used with caution, especially in patients with increased CVD risk. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Histopathological and Molecular Diagnostics)
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20 pages, 2455 KiB  
Review
The Role of MicroRNA in the Pathophysiology and Diagnosis of Viral Myocarditis
by Ewelina Młynarska, Krzysztof Badura, Szymon Kurciński, Julia Sinkowska, Paulina Jakubowska, Jacek Rysz and Beata Franczyk
Int. J. Mol. Sci. 2024, 25(20), 10933; https://doi.org/10.3390/ijms252010933 - 11 Oct 2024
Viewed by 1887
Abstract
Myocarditis is a non-ischemic condition with a heterogeneous etiology, clinical course and prognosis. The most common etiology of myocarditis are viral infections, whereas the most severe complications are acute and chronic heart failure and sudden cardiac death. The heterogeneous clinical course of the [...] Read more.
Myocarditis is a non-ischemic condition with a heterogeneous etiology, clinical course and prognosis. The most common etiology of myocarditis are viral infections, whereas the most severe complications are acute and chronic heart failure and sudden cardiac death. The heterogeneous clinical course of the disease, as well as the availability and costs of diagnostic tools such as cardiac magnetic resonance and endomyocardial biopsy, hinder the diagnosis of myocarditis and its underlying cause. Non-coding RNAs such as micro-RNAs (miRNAs; miR) have been shown to be involved in the disease’s pathophysiology; however, their potential in disease diagnosis and treatment should also be considered. Non-coding RNAs are RNAs that are not translated into proteins, and they have the ability to regulate several intracellular pathways. MiRNAs regulate gene expression by binding with their targets and inhibiting protein synthesis by interfering with the translation of coding genes or causing the degradation of messenger RNA. Several miRNAs, such as miR-1, -133, -21, -15, -98, -126, -155, -148, -203, -208, -221, -222, -203 and -590, have been shown to be involved in the pathophysiology of viral myocarditis (VMC), and some of them have been shown to have diagnostic abilities. This article summarizes the available data on miRNAs and their associations with VMC. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Histopathological and Molecular Diagnostics)
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Other

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9 pages, 32940 KiB  
Case Report
The Importance of Aortic Valve Bicuspid Phenotype in Valvular Evolution in Pediatric Patients: A Case Report and Literature Mini-Review
by Amalia Făgărășan, Simona Gurzu, Catalin-Bogdan Satala and Asmaa Carla Hagău
Int. J. Mol. Sci. 2023, 24(18), 14027; https://doi.org/10.3390/ijms241814027 - 13 Sep 2023
Cited by 2 | Viewed by 1551
Abstract
Bicuspid aortic valve (BAV) is the most commonly encountered congenital malformation in the pediatric population, associated with aortic leaflet degeneration and aortopathy. However, studies on BAV and its complications in children are limited. We present the case of a 16-year-old with type 1B [...] Read more.
Bicuspid aortic valve (BAV) is the most commonly encountered congenital malformation in the pediatric population, associated with aortic leaflet degeneration and aortopathy. However, studies on BAV and its complications in children are limited. We present the case of a 16-year-old with type 1B BAV with a raphe with fusion between the right and non-coronary cusps who exhibited severe aortic stenosis, regurgitation, and progressive dilatation of the ascending aorta. Surgical intervention, including aortic valve and aortic root replacement, was performed due to the patient’s deteriorating condition. Histopathological examination revealed degenerative changes and calcifications in the aortic valve and mucoid fibrosis in the ascending aorta. The results are consistent with BAV patients being predisposed to aortic stenosis and regurgitation due to increased mechanical stress and hemodynamic abnormalities. Although more common in adults and a rare complication in pediatric patients, calcification was previously observed concurrently with rapid valve degeneration in our daily practice. Further studies are needed to improve our understanding of the mechanisms underlying BAV-related complications and refine treatment strategies for pediatric patients. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Histopathological and Molecular Diagnostics)
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