Shanzuan Wang, Debin Zhuo, Juan Lin, Chunxia Zhang
{"title":"Key Genes and Biological Pathways in Pulmonary Arterial Hypertension Related to Endoplasmic Reticulum Stress Identified by Bioinformatics.","authors":"Shanzuan Wang, Debin Zhuo, Juan Lin, Chunxia Zhang","doi":"10.1097/FJC.0000000000001651","DOIUrl":"10.1097/FJC.0000000000001651","url":null,"abstract":"<p><strong>Abstract: </strong>Pulmonary arterial hypertension (PAH) is a cardiopulmonary vascular condition with an unclear pathogenesis. Targeting endoplasmic reticulum (ER) stress has been suggested as a novel treatment approach for PAH, but the mechanisms involving ER stress-related genes in PAH are not well understood. Microarray data for PAH and ER stress-related genes were analyzed. Differential and Venn analyses identified 17 differentially expressed ER stress-related genes in PAH. Candidate drugs targeting these genes were predicted using the CMap database. A protein-protein interaction (PPI) network was constructed, and hub genes (LCN2, IGF1, VCAM1, EDN1, HMOX1, TLR4) with complex interplays were identified using the STRING database and Cytoscape plugins. The clinical diagnostic performance of the hub genes was evaluated using ROC curves. The GeneMANIA Web site was utilized to predict enriched pathways associated with the hub genes and their functionally similar genes. MiRNAs and transcription factors targeting the hub genes were predicted using the Networkanalyst Web site. The immune levels in control samples and PAH samples were assessed using various algorithms. Nine drug candidates were found to potentially target the identified ER stress-related genes. The hub genes and their correlated genes were significantly enriched in immune-related pathways. The PAH group showed increased immune cell infiltration, indicating a heightened immune response. This study sheds light on the role of ER stress-associated hub genes in PAH and proposes potential drugs targeting these genes. These findings provide valuable insights into PAH mechanisms and support the exploration of ER stress as a therapeutic target.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":"85 2","pages":"108-119"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elissa Kerli Fernandes, Patrick Türck, Cristina Campos Carraro, Victor de Mello Palma, Gabriel de Lima Rosa, Adriana Simon Coitinho, Fernanda Visioli, Adriane Belló-Klein, Alexandre Luz de Castro, Alex Sander da Rosa Araujo
{"title":"Impact of Boldine Treatment on Hypertrophy and Lipid Peroxidation in the Right Ventricle Subjected to Experimental Adrenergic Overstimulation.","authors":"Elissa Kerli Fernandes, Patrick Türck, Cristina Campos Carraro, Victor de Mello Palma, Gabriel de Lima Rosa, Adriana Simon Coitinho, Fernanda Visioli, Adriane Belló-Klein, Alexandre Luz de Castro, Alex Sander da Rosa Araujo","doi":"10.1097/FJC.0000000000001657","DOIUrl":"10.1097/FJC.0000000000001657","url":null,"abstract":"<p><strong>Abstract: </strong>Adrenergic overstimulation is detrimental to the left ventricle. However, its effects on the right ventricle (RV) are not clear. Because adrenergic overload increases metabolic demand and oxidative stress, boldine could be a therapeutic option in the treatment of cardiovascular disease because of its antioxidant role. This study aimed to investigate the impact of adrenergic overload on RV remodeling and the cardioprotective effect of boldine. Animals were divided into 4 groups: control (C), boldine (25 mg/kg i. P .) (B), isoproterenol (ISO) (5 mg/kg subcutaneously), and boldine+isoproterenol (B+ISO). Echocardiography, Fulton index (FI), histology, oxidative stress, inflammation, and β-adrenergic receptor (ADR) were analyzed. The diastolic parasternal length [C 0.698 (0.623-0.724) versus ISO 0.77 (0.73-0.81)], FI [C 0.268 (0.231-0.275) versus ISO 0.340 (0.280-0.353)], inflammatory infiltration (∼40%), and ADR [C 0.78 (0.71-0.84) versus ISO 1.74 (1.52-2.00)] were increased in the ISO group ( P < 0.05). Boldine treatment (B+ISO) reduced the FI [0.240 (0.228-0.263)], lipid peroxidation [2.07 (2.01-2.61)], and ADR [0.71(0.62-0.80)]. Boldine increased total SH levels in B+ISO [C 2.4 (1.78-2.71); ISO 4.01 (2.95-4.66) versus B+ISO 6.77(5.15-8.60)] ( P < 0.05). There was a positive correlation between lipid peroxidation and the FI, and a negative correlation between total SH and the FI ( P < 0.05). This is the first study to explore the effects of adrenergic overstimulation on RV and the protective effect of boldine. Such data pave the way for further research involving RV remodeling, such as in pulmonary hypertension, and a new therapeutic option.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"166-175"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhengchao Li, Xingpeng Jiang, Jinghui Li, Yuzhu Wang
{"title":"Correlation of Hyaluronic Acid (HA), Syndecan-1 (SDC-1), Heparan Sulfate (HS) With Early Stage End Organ Dysfunction in Sepsis Patients.","authors":"Zhengchao Li, Xingpeng Jiang, Jinghui Li, Yuzhu Wang","doi":"10.1097/FJC.0000000000001654","DOIUrl":"10.1097/FJC.0000000000001654","url":null,"abstract":"<p><strong>Abstract: </strong>The aim of this study was to explore the relationship between the changes in early degradation products of polysaccharide coatings [such as hyaluronic acid (HA), syndecan-1 (SDC-1), and heparan sulfate (HS)] and the development of organ dysfunction in sepsis patients. We conducted a retrospective analysis on 140 sepsis patients admitted from January 2021 to June 2022, who formed the study group; 100 healthy individuals who underwent health checks during the same period were included as the control group. The study found that the expression levels of HA, SDC-1, and HS on admission and within 24 hours of admission in sepsis patients, as well as the early change rates, were positively correlated with organ dysfunction ( P < 0.05). Through receiver operating characteristic curve analysis, we discovered that the early change rates of HA, SDC-1, and HS have high predictive value for organ dysfunction in sepsis patients, with the combined predictive value being the most significant. The study conclusion points out that the increased levels of HA, SDC-1, HS, and other degradation products of polysaccharide coatings in the early stage of sepsis are positively associated with the occurrence of organ dysfunction. Clinicians can use the early expression changes of these biomarkers to predict the risk of organ dysfunction in sepsis patients, enabling timely implementation of preventive measures that may improve patient outcomes.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"129-136"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liu Yanjuan, Deng Shuangyou, Wang Ying, Chen Xing, Chen Yue, Yu Zixuan, Zhang Shumeng, Chen Lingli, Li Jie
{"title":"The Research Progress: Cuproptosis and Copper Metabolism in Regulating Cardiovascular Diseases.","authors":"Liu Yanjuan, Deng Shuangyou, Wang Ying, Chen Xing, Chen Yue, Yu Zixuan, Zhang Shumeng, Chen Lingli, Li Jie","doi":"10.1097/FJC.0000000000001653","DOIUrl":"10.1097/FJC.0000000000001653","url":null,"abstract":"<p><strong>Abstract: </strong>Studies have shown an association between cardiovascular disease and abnormal copper metabolism. Cuproptosis is caused by the accumulation of copper in vivo, and is a newly identified form of cell death. It regulates cardiovascular diseases by affecting vascular endothelial function and myocardial energy metabolism through pathways such as oxidative stress, mitochondrial function, and gene expression. The treatment of copper accumulation in Traditional Chinese Medicine primarily involves heat-clearing and detoxification therapy, supplemented with diuretic therapy. In contrast, Western medicine mainly uses copper chelators. Flavonoids are common active ingredients used in the treatment of copper metabolism-related and cardiovascular diseases. In this article, we reviewed the relationship between copper metabolism, cuproptosis, and cardiovascular disease, providing novel strategies for preventing and treating cardiovascular disease; our ultimate aim is to encourage inspiration and contemplation among readers.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"89-96"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142728963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bin Qi, Qing-Feng Wu, Zhi-Jie Yang, Nan Huang, Liu Miao
{"title":"Melatonin Attenuates Cardiac Dysfunction and Inflammation in Dilated Cardiomyopathy via M2 Macrophage Polarization.","authors":"Bin Qi, Qing-Feng Wu, Zhi-Jie Yang, Nan Huang, Liu Miao","doi":"10.1097/FJC.0000000000001650","DOIUrl":"10.1097/FJC.0000000000001650","url":null,"abstract":"<p><strong>Abstract: </strong>Melatonin is a neuroendocrine hormone that exerts protective effects on the heart. Increasing evidence suggests that macrophage M2-type polarization improves myocardial regeneration and repair. Therefore, this study investigated whether melatonin ameliorates dilated cardiomyopathy (DCM) by modulating M2-type polarization. DCM mice were established by induction with doxorubicin and then treated with melatonin. Cardiac dysfunction was determined by measuring left ventricular ejection fraction and left ventricular internal dimensions at end-diastole and end-systole. Heart injury and fibrosis were determined by hematoxylin and eosin staining and Sirius Red staining, respectively. Serum concentrations of melatonin, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) were measured through enzyme-linked immunosorbent assays. M2-type macrophages were analyzed by flow cytometry. Relative mRNA and protein levels were determined by reverse transcription quantitative polymerase chain reaction and Western blotting, respectively. Circulating melatonin levels were significantly decreased in DCM mice and were associated with left ventricular ejection fraction. Treatment with melatonin markedly ameliorated cardiac dysfunction, improved survival, and alleviated pathologic changes and collagen deposition in DCM mice. Furthermore, melatonin-treated DCM mice displayed lower serum and cardiac levels of IL-1β, IL-6, and TNF-α, as well as higher number of M2-type macrophages in cardiac tissue, indicating that melatonin treatment could decrease inflammatory responses and facilitate M2 macrophage polarization in DCM mice. Thus, melatonin treatment alleviated cardiac dysfunction and inflammatory responses by promoting M2 macrophage polarization in the DCM mouse model.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"156-165"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Antonio Abbate, Giuseppe Biondi-Zoccai, Raffaele Altara, George W Booz
{"title":"Changes for 2025 at Journal of Cardiovascular Pharmacology: Introducing Our Junior Associate Editors, Podcasts, Feature, and New Board Members.","authors":"Antonio Abbate, Giuseppe Biondi-Zoccai, Raffaele Altara, George W Booz","doi":"10.1097/FJC.0000000000001673","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001673","url":null,"abstract":"","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Julie Chugh, Jean Dai, Palika Datta, Kaytlin Krutsch
{"title":"Investigating the Transfer of Lisinopril Into Human Milk: A Quantitative Analysis.","authors":"Julie Chugh, Jean Dai, Palika Datta, Kaytlin Krutsch","doi":"10.1097/FJC.0000000000001642","DOIUrl":"10.1097/FJC.0000000000001642","url":null,"abstract":"<p><strong>Abstract: </strong>Lisinopril is commonly prescribed to manage conditions such as hypertension and heart failure. Although concerns about fetal toxicity have traditionally limited the use of lisinopril in women of reproductive age, recent American College of Obstetricians and Gynecologists guidelines promote aggressive treatment of hypertension, which may require the use of pharmacologic agents not previously considered in the postpartum period. We aimed to estimate infant exposure to maternal lisinopril through breast milk and report the tolerance of the breastfed infant. Five volunteers taking lisinopril provided samples of their human milk and their associated health information for research through the InfantRisk Center Human Milk Biorepository. The milk pharmacokinetics of lisinopril were measured using liquid chromatography-mass spectrometry. The mean milk concentration of lisinopril was 0.49 ng/mL per 10 mg daily dose. The relative infant dose was 0.06% for lisinopril, more than 100 times lower than the standard 10% safety threshold. The minimal transfer of lisinopril into human milk in this study suggests the drug is unlikely to pose a clinically significant risk to healthy breastfed infants.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"84-87"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transient Receptor Potential Canonical Channels in Cardiovascular Pathology and Their Modulators.","authors":"Hussein N Rubaiy","doi":"10.1097/FJC.0000000000001643","DOIUrl":"10.1097/FJC.0000000000001643","url":null,"abstract":"<p><strong>Abstract: </strong>Ion channels play a crucial role in various aspects of cardiac function, such as regulating rhythm and contractility. As a result, they serve as key targets for therapeutic interventions in cardiovascular diseases. Cell function is substantially influenced by the concentration of free cytosolic calcium (Ca 2+ ) and the voltage across the plasma membrane. These characteristics are known to be regulated by Ca 2+ -permeable nonselective cationic channels, although our knowledge of these channels is still inadequate. The transient receptor potential (TRP) superfamily comprises of many nonselective cation channels with diverse Ca 2+ permeability. Canonical or classical TRP (TRPC) channels are a subgroup of the TRP superfamily that are expressed ubiquitously in mammalian cells. TRPC channels are multidimensional signaling protein complexes that play essential roles in a variety of physiological and pathological processes in humans, including cancer, neurological disorders, cardiovascular diseases, and others. The objective of this article was to focus on the role that TRPC channels play in the cardiovascular system. The role of TRPC channels will be deeply discussed in cardiovascular pathology. Together, a critical element in developing novel treatments that target TRPC channels is comprehending the molecular mechanisms and regulatory pathways of TRPC channels in related cardiovascular diseases and conditions.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"21-34"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Run-Ze Tian, Dong-Lin Zhuang, Chi Teng Vong, Xuyu He, Qing Ouyang, Jing-Hua Liang, Yan-Ping Guo, Yu-Hong Wang, Shuang Zhao, Haiyun Yuan, Moussa Ide Nasser, Ge Li, Ping Zhu
{"title":"Role of Autophagy in Myocardial Remodeling After Myocardial Infarction.","authors":"Run-Ze Tian, Dong-Lin Zhuang, Chi Teng Vong, Xuyu He, Qing Ouyang, Jing-Hua Liang, Yan-Ping Guo, Yu-Hong Wang, Shuang Zhao, Haiyun Yuan, Moussa Ide Nasser, Ge Li, Ping Zhu","doi":"10.1097/FJC.0000000000001646","DOIUrl":"10.1097/FJC.0000000000001646","url":null,"abstract":"<p><strong>Abstract: </strong>Autophagy is the process of reusing the body's senescent and damaged cell components, which can be regarded as the cellular circulatory system. There are 3 distinct forms of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy. In the heart, autophagy is regulated mainly through mitophagy because of the metabolic changes of cardiomyocytes caused by ischemia and hypoxia. Myocardial remodeling is characterized by gradual heart enlargement, cardiac dysfunction, and extraordinary molecular changes. Cardiac remodeling after myocardial infarction is almost inevitable, which is the leading cause of heart failure. Autophagy has a protective effect on myocardial remodeling improvement. Autophagy can minimize cardiac remodeling by preventing misfolded protein accumulation and oxidative stress. This review summarizes the nestest molecular mechanisms of autophagy and myocardial remodeling, the protective effects, and the new target of autophagy medicine in cardiac remodeling. The future development and challenges of autophagy in heart disease are also summarized.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"1-11"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Athena Matsikas, Kassandra Marsh, Quy Huynh, Raymond Pashun, John Papadopoulos, Tania Ahuja
{"title":"Balancing the Interactions: Assessing Antiplatelet and Antiretroviral Therapy Drug-Drug Interactions in People Living With HIV.","authors":"Athena Matsikas, Kassandra Marsh, Quy Huynh, Raymond Pashun, John Papadopoulos, Tania Ahuja","doi":"10.1097/FJC.0000000000001638","DOIUrl":"10.1097/FJC.0000000000001638","url":null,"abstract":"<p><strong>Abstract: </strong>The clinical effect of drug-drug interactions (DDIs) between antiplatelets and antiretroviral therapy (ART) on bleeding, thrombosis, and other major adverse cardiovascular events (MACE) is unknown. The objective of this retrospective study was to assess the incidence of DDI at P2Y12 inhibitor (P2Y12inh) initiation and the effect of DDI on patient outcomes. Adult people living with HIV (PLWH) receiving ART newly initiated on an oral P2Y12inh were included. The primary outcome was the incidence of DDI between ART and P2Y12inh at P2Y12inh initiation. Secondary outcomes included bleeding events, MACE, and switches in P2Y12inh. There were 149 PLWH included, of these, 119 (80%) were initiated on clopidogrel, 23 (15%) on ticagrelor, and 7 (5%) on prasugrel. Ninety-three PLWH (60%) had a DDI at time of P2Y12inh initiation, with highest incidence in the clopidogrel group (n = 84, 71%), followed by ticagrelor (n = 9, 39%) and none with prasugrel. Within 1 year, MACE occurred in 12 PLWH, with DDI present at the time of 4 events. There were 29 bleeding events occurring within 1 year, including 17 events with DDI at time of event. However, 88% of DDI in patients with bleeding events were expected to decrease the efficacy of P2Y12inh. Though we observed high incidence of DDI between P2Y12inh and ART in PLWH, MACE and bleeding events at 1 year did not correlate with DDI. It remains unknown whether DDI presence at P2Y12inh initiation with ART causes clinical outcomes of concern, or whether underlying platelet reactivity in PLWH is associated with these events.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"75-83"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}