Effects of sex and obesity on immune checkpoint inhibition-related cardiac systolic dysfunction in aged mice DOI Creative Commons
Nabil V. Sayour, Dániel Kucsera,

Abdulaziz AlHaddad

и другие.

Basic Research in Cardiology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 8, 2024

Despite accumulating data on underlying mechanisms, the influence of sex and prevalent cardio-metabolic co-morbidities manifestation severity immune checkpoint inhibitor (ICI)-induced cardiotoxicity has not been well defined. To elucidate whether affect ICI-induced cardiotoxicity, we randomized 17-month-old male female mice to receive control diet (CON) or high-fat (HFD) + L-NAME-a well-established mouse model co-morbidities-for 17 weeks (n = 5-7), evaluated markers T-cell function in spleen. As expected, HFD L-NAME significantly increased body- heart weight, serum cholesterol levels, caused no systolic dysfunction, however, led diastolic cardiomyocyte hypertrophy, fibrosis only males compared corresponding CON. Western blot analyses splenic protein levels showed differential expression depending co-morbidities, suggesting exhaustion both sexes L-NAME, but more pronounced males. In a sub-study with similar setup, tested cardiotoxic manifestations ICI by treating anti-PD-1 monoclonal antibody (ICI) for last 2 administration 5-7). After treatment, cardiac functions decreased CON, groups baseline (before administration). conclusion, this exploratory study using aged mice, describe first time that ICI-related dysfunction is diminished when obesity hypercholesterolemia are present, possibly due obesity-related exhaustion.

Язык: Английский

An injectable conductive hydrogel restores electrical transmission at myocardial infarct site to preserve cardiac function and enhance repair DOI Creative Commons
Linghong Zhang, Tao Li,

Yan Yu

и другие.

Bioactive Materials, Год журнала: 2022, Номер 20, С. 339 - 354

Опубликована: Июнь 13, 2022

Myocardial infarction (MI) leads to massive cardiomyocyte death and deposition of collagen fibers. This fibrous tissue disrupts electrical signaling in the myocardium, leading cardiac systolic diastolic dysfunction, as well arrhythmias. Conductive hydrogels are a promising therapeutic strategy for MI. Here, we prepared highly water-soluble conductive material (GP) by grafting polypyrrole (PPy) onto non-conductive gelatin. component was added gel system formed Schiff base reaction between oxidized xanthan gum (OXG) gelatin construct an injectable hydrogel. The self-healing OGGP3 (3 wt% GP) hydrogel had good biocompatibility, elastic modulus, conductivity that matched natural heart. biomaterials were injected into rat myocardial scar 2 days after We found function rats treated with improved, making it more difficult induce resistivity reduced, conduction velocity increased. Histological analysis showed reduced infarct size, increased left ventricular wall thickness, vessel density, decreased inflammatory response infarcted area. Our findings clearly demonstrate attenuates remodeling inhibits dilation, thus showing its potential treatment

Язык: Английский

Процитировано

76
Myocardial ischemia/reperfusion: Translational pathophysiology of ischemic heart disease DOI Creative Commons
Gerd Heusch

Med, Год журнала: 2024, Номер 5(1), С. 10 - 31

Опубликована: Янв. 1, 2024

Ischemic heart disease is the greatest health burden and most frequent cause of death worldwide. Myocardial ischemia/reperfusion pathophysiological substrate ischemic disease. Improvements in prevention treatment have reduced mortality developed countries over last decades, but further progress now stagnant, morbidity from developing are increasing. Significant problems remain to be resolved require a better understanding. The present review attempts briefly summarize state art myocardial research, with view on both its coronary vascular aspects, define cutting edges where mechanistic knowledge needed facilitate translation clinical practice.

Язык: Английский

Процитировано

70
Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection DOI Creative Commons
Gerd Heusch, Ioanna Andreadou, Robert M. Bell

и другие.

Redox Biology, Год журнала: 2023, Номер 67, С. 102894 - 102894

Опубликована: Окт. 6, 2023

The present review summarizes the beneficial and detrimental roles of reactive oxygen species in myocardial ischemia/reperfusion injury cardioprotection. In first part, continued need for cardioprotection beyond that by rapid reperfusion acute infarction is emphasized. Then, pathomechanisms to myocardium coronary circulation different modes cell death are characterized. Different mechanical pharmacological interventions protect ischemic/reperfused elective percutaneous artery bypass grafting, cardiotoxicity from cancer therapy detailed. second part keeps focus on ROS providing a comprehensive overview molecular cellular mechanisms involved injury. Starting mitochondria as main sources targets myocardium, complex network extracellular processes discussed, including relationships with Ca2+ homeostasis, thiol group redox balance, hydrogen sulfide modulation, cross-talk NAPDH oxidases, exosomes, cytokines growth factors. While mechanistic insights needed improve our current therapeutic approaches, advancements knowledge ROS-mediated indicate facets oxidative stress opposed requirement physiological protective reactions. This inevitable contrast likely underlie unsuccessful clinical trials limits development novel cardioprotective simply based upon removal.

Язык: Английский

Процитировано

53
E-cardiac patch to sense and repair infarcted myocardium DOI Creative Commons

Renjie Qiu,

Xingying Zhang, Chen Song

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Май 16, 2024

Abstract Conductive cardiac patches can rebuild the electroactive microenvironment for infarcted myocardium but their repair effects benefit by carried seed cells or drugs. The key to success is effective integration of electrical stimulation with created conductive patches. Besides, due concerns in a high re-admission ratio heart patients, remote medicine device will underpin successful repair. Herein, we report miniature self-powered biomimetic trinity triboelectric nanogenerator unique double-spacer structure that unifies energy harvesting, therapeutics, and diagnosis one patch. Trinity improve electroactivity also wirelessly monitor electrocardiosignal mobile diagnosis. RNA sequencing analysis from rat hearts reveals this mainly regulates muscle contraction-, metabolism-, vascular regulation-related mRNA expressions vivo. research spawning truly integrates an functional patch e-care diagnostic sensor.

Язык: Английский

Процитировано

29
Mechanisms and clinical implications of endothelium-dependent vasomotor dysfunction in coronary microvasculature DOI
Sharif A. Sabe, Jun Feng, Frank W. Sellke

и другие.

AJP Heart and Circulatory Physiology, Год журнала: 2022, Номер 322(5), С. H819 - H841

Опубликована: Март 25, 2022

Coronary microvascular disease (CMD), which affects the arterioles and capillary endothelium that regulate myocardial perfusion, is an increasingly recognized source of morbidity mortality, particularly in setting metabolic syndrome. The coronary plays a pivotal role maintaining homeostasis, though factors such as diabetes, hypertension, hyperlipidemia, obesity can contribute to endothelial injury consequently arteriolar vasomotor dysfunction. These disturbances microvasculature clinically manifest diminished flow reserve, known independent risk factor for cardiac death, even absence macrovascular atherosclerotic disease. Therefore, growing body literature has examined molecular mechanisms by occurs at level consequences on responses. This review will begin with overview normal physiology, modalities measuring function, clinical implications CMD. introductory topics be followed discussion recent advances understanding inflammation, oxidative stress, insulin resistance, shear cell senescence, tissue ischemia dysregulate homeostasis function.

Язык: Английский

Процитировано

42
Early microvascular coronary endothelial dysfunction precedes pembrolizumab-induced cardiotoxicity. Preventive role of high dose of atorvastatin DOI Creative Commons
Panagiotis Efentakis,

Angeliki Choustoulaki,

Grzegorz Kwiatkowski

и другие.

Basic Research in Cardiology, Год журнала: 2024, Номер unknown

Опубликована: Март 23, 2024

Abstract Immune checkpoint inhibitors (ICIs) exhibit remarkable antitumor activity and immune-related cardiotoxicity of unknown pathomechanism. The aim the study was to investigate ICI class-dependent in vitro pembrolizumab’s (Pem’s) vivo, seeking for translational prevention means. Cytotoxicity investigated primary cardiomyocytes splenocytes, incubated with ipilimumab, Pem avelumab. Pem’s cross-reactivity assessed by circular dichroism (CD) on biotechnologically produced human murine PD-1 silico. C57BL6/J male mice received IgG4 or 2 5 weeks. Echocardiography, histology, molecular analyses were performed. Coronary blood flow velocity mapping cardiac magnetic resonance imaging conducted at Human EA.hy926 endothelial cells Pem-conditioned media from mononuclear cells, presence absence statins viability signaling assessed. Atorvastatin (20 mg/kg, daily) administered vivo , as prophylaxis. Only exerted cytotoxicity vitro. confirmed CD docking. In initiated coronary diastolic dysfunction weeks systolic At weeks, induced ICAM-1 iNOS expression intracardiac leukocyte infiltration. exacerbated activation triggered inflammation. led which prevented atorvastatin. mitigated functional deficits, inhibiting vivo. We established first time an model Pem-induced cardiotoxicity. precedes cardiotoxicity, whereas atorvastatin emerges a novel prophylactic therapy.

Язык: Английский

Процитировано

15
Safety and efficacy of platelet-derived mitochondrial transplantation in ischaemic heart disease DOI
Fatemeh Baharvand,

Mehryar Habibi Roudkenar,

Zahra Pourmohammadi-Bejarpasi

и другие.

International Journal of Cardiology, Год журнала: 2024, Номер 410, С. 132227 - 132227

Опубликована: Июнь 5, 2024

Язык: Английский

Процитировано

11
Microenvironment‐Regulated Hydrogels Prepared with a Brand‐New Small Molecule Cross‐Linker for Stepwise Treatment of Myocardial Infarction DOI Open Access

Yu Wu,

Wen Zhang, Linlin Huang

и другие.

Advanced Healthcare Materials, Год журнала: 2025, Номер unknown

Опубликована: Март 4, 2025

Abstract Despite the development of many injectable hydrogels intended for repair myocardial infarction (MI), their effectiveness is often compromised because they target merely one or two phases MI's pathological progression. Here, a multifunctional hydrogel delivery platform prepared with brand‐new small molecule cross‐linker stepwise treatment MI. The synthesis and reporting novel small‐molecule phenylboronic acid ((N(BA) 3 )) precise molecular structure conducted first time, it successfully utilized polyvinyl alcohol (PVA) dopamine to prepare infarct microenvironmental responsiveness anti‐oxidant. Further, considering multistage MI repair, contains both hyperoside bioactive nanoparticles (EGCG@Hyp&Arg NPs) PLGA microspheres loaded galunisertib (PLGA@Gal Ms). EGCG@Hyp&Arg NPs are rapidly released demonstrate anti‐inflammatory pro‐angiogenesis effects, while in long term, Gal from PLGA@Gal Ms inhibit fibrosis improve cardiac function. Results vitro vivo studies reveal that engineered programmed capabilities anti‐oxidation, reducing inflammation, promoting new blood vessel formation, inhibiting fibrosis, thereby significantly enhancing heart function post‐MI. Overall, this has great potential application as therapeutic strategy

Язык: Английский

Процитировано

1
Machine learning enabled multiscale model for nanoparticle margination and physiology based pharmacokinetics DOI Creative Commons

Sahil Kulkarni,

Benjamin Lin, Ravi Radhakrishnan

и другие.

Computers & Chemical Engineering, Год журнала: 2025, Номер unknown, С. 109081 - 109081

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

1
Myocardial injury, troponin release, and cardiomyocyte death in brief ischemia, failure, and ventricular remodeling DOI
John M. Canty

AJP Heart and Circulatory Physiology, Год журнала: 2022, Номер 323(1), С. H1 - H15

Опубликована: Май 13, 2022

Troponin released from irreversibly injured myocytes is the gold standard biomarker for rapid identification of an acute coronary syndrome. In myocardial infarction, necrotic cell death characterized by sarcolemmal disruption in response to a critical level energy depletion after more than 15 min ischemia. Although troponin I and T are highly specific cardiomyocyte death, high-sensitivity assays have demonstrated that measurable circulating levels present many normal subjects. addition, transient as well chronic elevations been disease states not clearly associated with The latter observations given rise clinical concept injury. This review will summarize evidence supporting notion parallel extent myocyte apoptosis ventricular remodeling pathophysiological conditions infarction or necrosis. It can be accelerated diastolic strain elevated preload systolic dyskinesis brief episodes ischemia too short cause depletion. We then show how chronic, low rates endogenous turnover, repetitive ischemia, left pressure lead significant loss absence neurohormonal stimulation. Finally, we posit differential strain-induced injury heart failure may determine whether progressive reduced ejection fraction interstitial fibrosis preserved become phenotype.

Язык: Английский

Процитировано

31