ABSTRACT

OBJECTIVES: Cisplatin (CP) is frequently used in various types of cancers. The cardiotoxic effects of this agent limit its usage. Our study seeks to investigate the protective effects of Irbesartan (IRB) on CP-induced cardiotoxicity.

MATERIALS AND METHODS: The following four groups comprised thirty-two rats: control, CP, CP+IRB, and IRB. On the fourth day of the experiment, 5 mg/kg of CP was given to CP and CP+IRB groups intraperitoneally, and for seven days, water or IRB 50 mg/kg (orally) was administered. Vascular endothelial growth factor (VEGF), caspase-3 (Cas-3), vascular cell adhesion molecule-1 (VCAM-1), NADPH oxidase-1 (NOX-1), creatine kinase MB (CK-MB), and lactate dehydrogenase (LDH) were measured.

RESULTS: The levels of VCAM-1, NOX-1, VEGF, Cas-3, and LDH were increased in the CP group. The treatment with IRB decreased VCAM-1, NOX-1, VEGF, Cas-3, and LDH levels significantly (P0.05). Histopathological examination revealed normal heart architecture in Control and IRB groups. While marked hyperemia and myocardial cell degeneration were noticed in the CP group, significant amelioration was observed in the CP+IRB group. Aortas in the CP group showed endothelial damage and desquamation. IRB treatment markedly ameliorated histopathological findings in the CP+IRB group. Cardiac and aortic damage caused by CP was attenuated by IRB treatment owing to the anti-inflammatory and antiapoptotic effects of IRB.

CONCLUSION: IRB may help reduce the severity of CP-induced cardiac injury by limiting leukocyte migration and reducing inflammation and apoptosis.

PMID:37885998 | PMC:PMC10598814 | DOI:10.22038/IJBMS.2023.70997.15422

23:06

PubMed articles on: Cardio-Oncology

The (pro)renin Receptor - A Regulatory Nodal Point in Disease Networks

Curr Drug Targets. 2023 Oct 25. doi: 10.2174/0113894501250617231016052930. Online ahead of print.

ABSTRACT

Experimental inhibition of the (pro)renin receptor [(P)RR] is a promising therapeutic strategy in different disease models ranging from cardiorenal to oncological entities. Here, we briefly review the direct protein-protein interaction partners of the (P)RR and the plethora of distinct diseases in which the (P)RR is involved. The first structural work on the (P)RR using AlphaFold, which was recently published by Ebihara et al., is the center of this mini-review since it can mechanistically link the protein-protein interaction level with the pathophysiological level. More detailed insights into the 3D structure of the (P)RR and its interaction domains might guide drug discovery on this novel target. Finally, antibody- and small molecule-based approaches to inhibit the (P)RR are shortly discussed.

PMID:37885110 | DOI:10.2174/0113894501250617231016052930

23:06

PubMed articles on: Cardio-Oncology

Thymus alterations and susceptibility to immune checkpoint inhibitor myocarditis

Nat Med. 2023 Oct 26. doi: 10.1038/s41591-023-02591-2. Online ahead of print.

ABSTRACT

Immune checkpoint inhibitors (ICI) have transformed the therapeutic landscape in oncology. However, ICI can induce uncommon life-threatening autoimmune T-cell-mediated myotoxicities, including myocarditis and myositis. The thymus plays a critical role in T cell maturation. Here we demonstrate that thymic alterations are associated with increased incidence and severity of ICI myotoxicities. First, using the international pharmacovigilance database VigiBase, the Assistance Publique Hôpitaux de Paris-Sorbonne University data warehouse (Paris, France) and a meta-analysis of clinical trials, we show that ICI treatment of thymic epithelial tumors (TET, and particularly thymoma) was more frequently associated with ICI myotoxicities than other ICI-treated cancers. Second, in an international ICI myocarditis registry, we established that myocarditis occurred earlier after ICI initiation in patients with TET (including active or prior history of TET) compared to other cancers and was more severe in terms of life-threatening arrythmias and concurrent myositis, leading to respiratory muscle failure and death. Lastly, we show that presence of anti-acetylcholine-receptor antibodies (a biological proxy of thymic-associated autoimmunity) was more prevalent in patients with ICI myocarditis than in ICI-treated control patients. Altogether, our results highlight that thymic alterations are associated with incidence and seriousness of ICI myotoxicities. Clinico-radio-biological workup evaluating the thymus may help in predicting ICI myotoxicities.

PMID:37884625 | DOI:10.1038/s41591-023-02591-2

23:07

PubMed articles on: Cardio-Oncology

Cancer and Atrial Fibrillation Comorbidities Among 25 Million Citizens in Shanghai, China: Medical Insurance Database Study

JMIR Public Health Surveill. 2023 Oct 17;9:e40149. doi: 10.2196/40149.

ABSTRACT

BACKGROUND: With population aging, the prevalence of both cancer and atrial fibrillation (AF) have increased. However, there is scarce epidemiological data concerning the comorbid state of cancer and AF in low- and middle-income countries, including China.

OBJECTIVE: We aimed to evaluate the site-, sex-, and age-specific profiles of cancer and AF comorbidities in Chinese populations.

METHODS: Data from the Shanghai Municipal Health Commission database between 2015 and 2020 were screened, covering all medical records of Shanghai residents with medical insurance. Site-specific cancer profiles were evaluated for the population with AF relative to the age- and sex-adjusted population of residents without AF. The sex distribution and peak age of cancer diagnosis were also assessed.

RESULTS: A total of 25,964,447 adult patients were screened. Among them, 22,185 patients presented cancers comorbid with AF (median 77, IQR 67-82 years of age; men: n=13,631, 61.44%), while 839,864 presented cancers without AF (median 67, IQR 57-72 years of age; men: n=419,020, 49.89%), thus yielding a higher cancer prevalence among residents with AF (8.27%) than among those without AF (6.05%; P<.001).

CONCLUSIONS: Patients with AF are associated with increased prevalence, heightened male predominance, and younger peak age of cancer. Further studies are needed to determine whether early screening of specific cancers is cost-effective and beneficial for patients with AF.

PMID:37847541 | DOI:10.2196/40149

23:07

PubMed articles on: Cardio-Oncology

Association of chronic kidney disease with cardiovascular disease in cancer patients: a cross-sectional study

Cardiorenal Med. 2023 Oct 14. doi: 10.1159/000534182. Online ahead of print.

ABSTRACT

INTRODUCTION: Due to the cardiotoxicity of cancer treatment and traditional risk factors for cardiovascular disease (CVD) such as obesity, diabetes, dyslipidemia, and hypertension, cancer patients are at higher risk of developing CVD. However, limited research exists on the correlation between chronic kidney disease (CKD) and CVD risk in cancer patients.

METHODS: This cross-sectional study selected cancer patients aged ≥20 years from the National Health and Nutrition Examination Survey (NHANES) conducted from 2015 to 2020. Multivariable logistic regression was used to assess the association between CKD and CVD in cancer patients. Additionally, subgroup analyses were conducted to investigate the association among different groups of cancer patients.

RESULTS: We included 1700 adult cancer patients (52.53% were female). After multivariable adjustment for covariates including traditional CVD factors, CKD was significantly associated with CVD, with an odds ratio (95% confidence interval) and P-value of 1.61(1.18,2.19) and 0.004. Subgroup analyses after multivariable adjustment showed a significant correlation between CKD and increased CVD risk in the following populations: age ≥60 years, males, White ethnicity, and individuals with or without traditional CVD factors (obesity, diabetes, dyslipidemia, and hypertension).

CONCLUSIONS: CKD remains a significant factor in the higher risk of CVD among adult cancer patients in the United States, even after adjustment for traditional CVD risk factors. Therefore, to reduce the risk of CVD in cancer patients, it is important to treat CKD as a non-traditional risk factor for CVD and actively manage it.

PMID:37839394 | DOI:10.1159/000534182

23:07

PubMed articles on: Cardio-Oncology

ATP protects anti-PD-1/radiation-induced cardiac dysfunction by inhibiting anti-PD-1 exacerbated cardiomyocyte apoptosis, and improving autophagic flux

Heliyon. 2023 Oct 5;9(10):e20660. doi: 10.1016/j.heliyon.2023.e20660. eCollection 2023 Oct.