Special Issue "Novel Translational Approaches to the Treatment of Coronary Artery Disease and Congenital Heart Disease in Comorbid Patients"

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmaceutical Technology".

Deadline for manuscript submissions: closed (15 October 2020).

Special Issue Editor

Dr. Anton G. Kutikhin
E-Mail Website
Guest Editor
Head of the Laboratory for Vascular Biology, Division of Experimental Medicine, Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russia
Interests: vascular biology; atherosclerosis; endothelial dysfunction; intimal hyperplasia; vascular inflammation; vasa vasorum; calcification; calciprotein particles
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Special Issue Information

Dear Colleagues,

Current advances in the treatment of cardiovascular disease have become possible primarily owing to the synergy among vascular biology, vascular tissue engineering, and translational and clinical medicine. Discoveries made on the bench are now efficiently translated into preclinical testing on conventional and genetically modified animal models, and the most significant breakthroughs enter the clinical trials. However, aging of the population, characterized by a large proportion of patients having co-occurring diseases (multiple morbidities), represents a major challenge for cardiovascular medicine and requires significant efforts to improve the outcome.

Rapid development of visualization techniques, including molecular imaging, has provided unique insights into cardiovascular pathology and identified a number of promising therapeutic targets. Further, it has allowed the implementation of novel surgical modalities employing vascular tissue engineering products, for instance, biodegradable vascular grafts, drug-eluting stents, and bioprosthetic heart valves. The advent and dissemination of high-throughput approaches to analyze the genome, transcriptome, proteome, and metabolome have resulted in significant discoveries in vascular biology which has conceptualized our understanding of the cardiovascular system and suggested the potential culprits of cardiovascular disease. Active interactions between basic scientists, clinicians, industry, and policy makers have cumulatively led to a lot of perspective projects, the results of which have only recently been obtained or are being expected in the nearest future.

The present Special Issue aims to summarize the newest advances in cardiovascular translational research with respect to comorbid patients which represent a clinical setting increasingly becoming more and more important. It highlights the most promising therapeutic targets found in pathophysiology studies and novel efficient surgical interventions. Importantly, it also sheds light on recent advances in vascular tissue engineering, in particular, preclinical development of small-diameter vascular prostheses and transcatheter heart valves. The issue contains both exemplary original research studies and comprehensive review articles critically discussing the existing knowledge in the field.

Dr. Anton G. Kutikhin
Guest Editor

Manuscript Submission Information

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Keywords

  • Heart
  • Blood vessels
  • Cardiovascular disease
  • Coronary artery disease
  • Ischemic heart disease
  • Coronary heart disease
  • Acute coronary syndrome
  • Angina pectoris
  • Stable angina
  • Unstable angina
  • Myocardial infarction
  • Cardiac arrhythmia
  • Atrial fibrillation
  • Ventricular fibrillation
  • Heart block
  • Heart failure
  • Congenital heart disease
  • Tetralogy of fallot
  • Comorbidity
  • Multimorbidity
  • Multiple morbidities
  • Comorbid patients
  • Overweight
  • Obesity
  • Diabetes mellitus
  • Chronic obstructive pulmonary disease
  • Chronic kidney disease
  • Cognitive impairment
  • Myocardial revascularization
  • Percutaneous coronary intervention
  • Coronary artery bypass graft surgery
  • Preclinical development
  • Animal testing
  • Clinical trials
  • Vascular tissue engineering
  • Cognitive therapy
  • Cardiac remodeling
  • Cardiac fibrosis
  • Cardiac regeneration
  • Endothelial dysfunction
  • Atherosclerosis
  • In-stent restenosis
  • Thrombosis
  • Intimal hyperplasia
  • Vascular inflammation
  • Calcification
  • Plaque rupture
  • Cardiomyocytes
  • (myo)fibroblasts
  • Endothelium
  • Vascular smooth muscle cells
  • Macrophages
  • Epicardial adipose tissue
  • Perivascular adipose tissue
  • Subcutaneous adipose tissue
  • Platelets

Published Papers (5 papers)

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Research

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Article
bFGF and SDF-1α Improve In Vivo Performance of VEGF-Incorporating Small-Diameter Vascular Grafts
Pharmaceuticals 2021, 14(4), 302; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14040302 - 28 Mar 2021
Viewed by 488
Abstract
Tissue-engineered vascular grafts are widely tested as a promising substitute for both arterial bypass and replacement surgery. We previously demonstrated that incorporation of VEGF into electrospun tubular scaffolds from poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(ε-caprolactone) enhances formation of an endothelial cell monolayer. However, an overdose of VEGF can [...] Read more.
Tissue-engineered vascular grafts are widely tested as a promising substitute for both arterial bypass and replacement surgery. We previously demonstrated that incorporation of VEGF into electrospun tubular scaffolds from poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(ε-caprolactone) enhances formation of an endothelial cell monolayer. However, an overdose of VEGF can induce tumor-like vasculature; thereby, other bioactive factors are needed to support VEGF-driven endothelialization and successful recruitment of smooth muscle cells. Utilizing emulsion electrospinning, we fabricated one-layer vascular grafts with either VEGF, bFGF, or SDF-1α, and two-layer vascular grafts with VEGF incorporated into the inner layer and bFGF and SDF-1α incorporated into the outer layer with the following structural evaluation, tensile testing, and in vivo testing using a rat abdominal aorta replacement model. The latter graft prototype showed higher primary patency rate. We found that the two-layer structure improved surface topography and mechanical properties of the grafts. Further, the combination of bFGF, SDF-1α, and VEGF improved endothelialization compared with VEGF alone, while bFGF induced a rapid formation of a smooth muscle cell layer. Taken together, these findings show that the two-layer structure and incorporation of bFGF and SDF-1α into the vascular grafts in combination with VEGF provide a higher primary patency and therefore improved in vivo performance. Full article
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Article
Resistance to Acetylsalicylic Acid in Patients with Coronary Heart Disease Is the Result of Metabolic Activity of Platelets
Pharmaceuticals 2020, 13(8), 178; https://0-doi-org.brum.beds.ac.uk/10.3390/ph13080178 - 01 Aug 2020
Cited by 1 | Viewed by 1145
Abstract
Sensitivity to acetylsalicylic acid (ASA) is important in the treatment of patients with coronary heart disease (CHD) after coronary artery bypass grafting (CABG). Patients were divided into ASA sensitive (sASA) and ASA resistant (rASA) by the activity of platelet aggregation induced arachidonic acid [...] Read more.
Sensitivity to acetylsalicylic acid (ASA) is important in the treatment of patients with coronary heart disease (CHD) after coronary artery bypass grafting (CABG). Patients were divided into ASA sensitive (sASA) and ASA resistant (rASA) by the activity of platelet aggregation induced arachidonic acid (ARA) together with ASA. Induced platelet aggregation activity was studied in sASA and rASA patients with CHD before and after CABG. The level of synthesis of primary and secondary reactive oxygen species (ROS) by platelets was determined using chemiluminescent analysis. The activity of NAD- and NADP-dependent dehydrogenases in platelets was determined by the bioluminescent method. It was found that the aggregation activity of platelets depended on the sensitivity of CHD patients to ASA and decreased during postoperative ASA therapy. The most pronounced differences in metabolic parameters of platelets in sASA and rASA patients were detected by Nox2 activity. The synthesis of secondary ROS by platelets of CHD patients did not depend on the sensitivity of patients to ASA but increased during postoperative treatment with ASA. The activity of NAD(P)-dependent dehydrogenases in platelets did not differ in sASA and rASA patients with CHD. Full article
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Article
Peculiarities of Platelet Metabolism in Patients with Acute Coronary Syndrome with Anxiety–Depressive Disorders and Informativity of Enzymes in the Forecast of Development of Cardiovascular Complications
Pharmaceuticals 2020, 13(8), 169; https://0-doi-org.brum.beds.ac.uk/10.3390/ph13080169 - 28 Jul 2020
Cited by 1 | Viewed by 628
Abstract
Anxiety–depressive disorders (ADD) are a risk factor of cardiovascular mortality in patients with coronary artery disease (CAD). Acute coronary syndrome (ACS) is the main clinical manifestation of a progressing CAD. Metabolic processes disorder in platelets can be one of the causes of cardiovascular [...] Read more.
Anxiety–depressive disorders (ADD) are a risk factor of cardiovascular mortality in patients with coronary artery disease (CAD). Acute coronary syndrome (ACS) is the main clinical manifestation of a progressing CAD. Metabolic processes disorder in platelets can be one of the causes of cardiovascular complications in patients with ACS and concomitant ADD. We studied platelets metabolism and prognostic informativity of NAD(P)-dependent dehydrogenases of platelets in ACS patients with ADD in terms of forecasting cardiovascular complications development over a year of observation. The levels of NAD- and NADP-dependent dehydrogenases of platelets were determined by means of a bioluminescent method during the first 24 h after admission to hospital and in dynamics in 10 days. Among 315 examined patients, ADD was found in 161 (51.1%). ACS patients with concomitant ADD had both cytoplasmic and mitochondrial processes impairment in platelets that consisted in a decrease of energy metabolism intensity, inhibition of anaerobic glycolysis reactions and lipid catabolism. After 12 months of follow-up, 41 (25.5%) cardiovascular complications were detected in the group of ACS patients with ADD and 20 (13.0%) in the group of ACS patients without ADD. According to the results of the analysis of the neural network based on NAD(P)-dependent dehydrogenases of platelets activity in ACS patients with ADD, indicators were obtained that are informative for predicting the development of recurrent cardiovascular complications. Full article
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Communication
A Brief Report on an Implantation of Small-Caliber Biodegradable Vascular Grafts in a Carotid Artery of the Sheep
Pharmaceuticals 2020, 13(5), 101; https://0-doi-org.brum.beds.ac.uk/10.3390/ph13050101 - 21 May 2020
Cited by 5 | Viewed by 972
Abstract
The development of novel biodegradable vascular grafts of a small diameter (<6 mm) is an unmet clinical need for patients requiring arterial replacement. Here we performed a pre-clinical study of new small-caliber biodegradable vascular grafts using a sheep model of carotid artery implantation. [...] Read more.
The development of novel biodegradable vascular grafts of a small diameter (<6 mm) is an unmet clinical need for patients requiring arterial replacement. Here we performed a pre-clinical study of new small-caliber biodegradable vascular grafts using a sheep model of carotid artery implantation. The 4 mm diameter vascular grafts were manufactured using a mix of polyhydroxybutyrate/valerate and polycaprolactone supplemented with growth factors VEGF, bFGF and SDF-1α (PHBV/PCL-GFmix) and additionally modified by a polymer hydrogel coating with incorporation of drugs heparin and iloprost (PHBV/PCL-GFmixHep/Ilo). Animals with carotid artery autograft implantation and those implanted with clinically used GORE-TEX® grafts were used as control groups. We observed that 24 h following surgery, animals with carotid artery autograft implantation showed 87.5% patency, while all the PHBV/PCL-GFmix and GORE-TEX® grafts displayed thrombosis. PHBV/PCL-GFmixHep/Ilo grafts demonstrated 62.5% patency 24 h following surgery and it had remained at 50% 1 year post-operation. All the PHBV/PCL grafts completely degraded less than 1 year following surgery and were replaced by de novo vasculature without evidence of calcification. On the other hand, GORE-TEX® grafts displayed substantial amounts of calcium deposits throughout graft tissues. Thus, here we report a potential clinical usefulness of PHBV/PCL grafts upon their additional modification by growth factors and drugs to promote endothelialization and reduce thrombogenicity. Full article
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Case Report
What the Cardiologist Needs to Consider in the Management of Oncologic Patients with STEMI-Like Syndrome: A Case Report and Literature Review
Pharmaceuticals 2021, 14(6), 563; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060563 - 12 Jun 2021
Cited by 1 | Viewed by 772
Abstract
In pre-hospital care, an accurate and quick diagnosis of ST-segment elevation myocardial infarction (STEMI) is imperative to promptly kick-off the STEMI network with a direct transfer to the cardiac catheterization laboratory (cath lab) in order to reduce myocardial infarction size and mortality. Aa [...] Read more.
In pre-hospital care, an accurate and quick diagnosis of ST-segment elevation myocardial infarction (STEMI) is imperative to promptly kick-off the STEMI network with a direct transfer to the cardiac catheterization laboratory (cath lab) in order to reduce myocardial infarction size and mortality. Aa atherosclerotic plaque rupture is the main mechanism responsible for STEMI. However, in a small percentage of patients, emergency coronarography does not reveal any significant coronary stenosis. The fluoropyrimidine agents such as 5-Fluorouracil (5-FU) and capecitabine, widely used to treat gastrointestinal, breast, head and neck cancers, either as a single agent or in combination with other chemotherapies, can cause potentially lethal cardiac side effects. Here, we present the case of a patient with 5-FU cardiotoxicity resulting in an acute coronary syndrome (ACS) with recurrent episodes of chest pain and ST-segment elevation.. Our case report highlights the importance of widening the knowledge among cardiologists of the side effects of chemotherapeutic drugs, especially considering the rising number of cancer patients around the world and that fluoropyrimidines are the main treatment for many types of cancer, both in adjuvant and advanced settings. Full article
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