Interaction of Cardiovascular Nonmodifiable Risk Factors, Comorbidities and Comedications With Ischemia/Reperfusion Injury and Cardioprotection by Pharmacological Treatments and Ischemic Conditioning

Pharmacological Reviews, Journal Year: 2022, Volume and Issue: 75(1), P. 159 - 216

Published: Dec. 8, 2022

Preconditioning, postconditioning, and remote conditioning of the myocardium enhance ability heart to withstand a prolonged ischemia/reperfusion insult potential provide novel therapeutic paradigms for cardioprotection. While many signaling pathways leading endogenous cardioprotection have been elucidated in experimental studies over past 30 years, no cardioprotective drug is on market yet that indication. One likely major reason this failure translate into patient benefit lack rigorous systematic preclinical evaluation promising therapies prior their clinical evaluation, since ischemic disease humans complex disorder caused by or associated with cardiovascular risk factors comorbidities. These comorbidities induce fundamental alterations cellular cascades affect development injury responses interventions. Moreover, some medications used treat these may impact again modifying pathways. The aim article review recent evidence as well modify response We emphasize critical need taking account presence concomitant when designing identification validation targets studies. This will hopefully maximize success rate developing rational approaches effective majority patients multiple

Significance Statement

Ischemic cause mortality; however, there are still drugs market. Most undertaken animal models absence comorbidities; develops other systemic disorders (e.g., hypertension, hyperlipidemia, diabetes, atherosclerosis). Here we focus showing how routine interfere strategies.

Language: Английский

---

Coronary blood flow in heart failure: cause, consequence and bystander

Basic Research in Cardiology, Journal Year: 2022, Volume and Issue: 117(1)

Published: Jan. 13, 2022

Heart failure is a clinical syndrome where cardiac output not sufficient to sustain adequate perfusion and normal bodily functions, initially during exercise in more severe forms also at rest. The two most frequent are heart of ischemic origin non-ischemic origin. In origin, reduced coronary blood flow causal contractile dysfunction, this true for stunned hibernating myocardium, microembolization, myocardial infarction post-infarct remodeling, possibly the takotsubo syndrome. form dilated cardiomyopathy, caused by genetic mutations, myocarditis, toxic agents or sustained tachyarrhythmias, alterations result from contribute dysfunction. Hypertrophic cardiomyopathy mutations but can increased pressure volume overload (hypertension, valve disease). with preserved ejection fraction characterized pronounced microvascular contribution which however clear. present review characterizes causes consequences its different manifestations. Apart any potentially accompanying atherosclerosis, all entities share common features impaired flow, extent: enhanced extravascular compression, nitric oxide-mediated, endothelium-dependent vasodilation vasoconstriction mediators neurohumoral activation. Impaired contributes progression thus valid target established novel treatment regimens.

Language: Английский

---

Myocardial ischemia/reperfusion: Translational pathophysiology of ischemic heart disease

Med, Journal Year: 2024, Volume and Issue: 5(1), P. 10 - 31

Published: Jan. 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.

Language: Английский

---

Coronary microvascular obstruction and dysfunction in patients with acute myocardial infarction

Nature Reviews Cardiology, Journal Year: 2023, Volume and Issue: 21(5), P. 283 - 298

Published: Nov. 24, 2023

Language: Английский

---

Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection

Redox Biology, Journal Year: 2023, Volume and Issue: 67, P. 102894 - 102894

Published: Oct. 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.

Language: Английский

---

Macrophage profiling in atherosclerosis: understanding the unstable plaque

Basic Research in Cardiology, Journal Year: 2024, Volume and Issue: 119(1), P. 35 - 56

Published: Jan. 20, 2024

Language: Английский

---

Large and Small Animal Models of Heart Failure With Reduced Ejection Fraction

Circulation Research, Journal Year: 2022, Volume and Issue: 130(12), P. 1888 - 1905

Published: June 9, 2022

Heart failure (HF) describes a heterogenous complex spectrum of pathological conditions that results in structural and functional remodeling leading to subsequent impairment cardiac function, including either systolic dysfunction, diastolic or both. Several factors chronically lead HF, volume pressure overload may result from hypertension, valvular lesions, acute, chronic ischemic injuries. Major forms HF include hypertrophic, dilated, restrictive cardiomyopathy. The severity cardiomyopathy can be impacted by other comorbidities such as diabetes obesity external stress factors. Age is another major contributor, the number patients with rising worldwide part due an increase aged population. occur reduced ejection fraction (HF fraction), is, overall function compromised, typically left ventricular lower than 40%. In some cases preserved fraction). Animal models play critical role facilitating understanding molecular mechanisms how hearts fail. This review aims summarize describe strengths, limitations, outcomes both small large animal are currently used basic translational research. driving defect heart adequately supply tissues blood impaired filling pumping. An accurate model would encompass symptoms (fatigue, dyspnea, exercise intolerance, edema) along pathology (collagen fibrosis, hypertrophy) ultimately exhibit decrease output. Although countless experimental studies have been published, no completely recapitulates full human disease. Therefore, it evaluate strength weakness each allow better selection what use address scientific question proposed.

Language: Английский

---

Targeting PDE4B (Phosphodiesterase-4 Subtype B) for Cardioprotection in Acute Myocardial Infarction via Neutrophils and Microcirculation

Circulation Research, Journal Year: 2022, Volume and Issue: 131(5), P. 442 - 455

Published: July 28, 2022

Background: Timely and complete restoration of blood flow is the most effective intervention for patients with acute myocardial infarction. However, efficacy limited by ischemia-reperfusion (MI/R) injury. PDE4 (phosphodiesterase-4) hydrolyzes intracellular cyclic adenosine monophosphate it has 4 subtypes A-D. This study aimed to delineate role PDE4B (phosphodiesterase-4 subtype B) in MI/R Methods: Mice were subjected 30-minute coronary artery ligation, followed 24-hour reperfusion. Cardiac perfusion was assessed laser Doppler flow. Vasomotor reactivities determined mouse human (micro-)arteries. Results: expression PDE4B, but not other subtypes, increased mice following detected primarily endothelial myeloid cells hearts. deletion strikingly reduced infarct size improved cardiac function or 28-day after MI/R. bone marrow–derived promoted injury vascular further exaggerated this Mechanistically, mediated neutrophil-endothelial cell interaction PKA (protein kinase A)-dependent adhesion molecules, neutrophil infiltration, release proinflammatory cytokines. Meanwhile, microcirculatory obstruction permeability MI/R, without affecting restriction-induced thrombosis. blockade flow-mediated vasodilatation endothelium-dependent dilatation arteries a PKA- nitric oxide–dependent manner. Furthermore, postischemia administration piclamilast, pan-inhibitor, microcirculation, suppressed inflammation, attenuated mice. Incubation sera from infarction impaired acetylcholine-induced relaxations microarteries, which abolished inhibition. Similar protection against MI/R-related recapitulated inhibition, pure vasodilator, sodium nitroprusside. Conclusions: critically involved inflammation microvascular obstruction, leading Selective inhibition might protect designated reperfusion therapy.

Language: Английский

---

Mechanisms and clinical implications of endothelium-dependent vasomotor dysfunction in coronary microvasculature

AJP Heart and Circulatory Physiology, Journal Year: 2022, Volume and Issue: 322(5), P. H819 - H841

Published: March 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.

Language: Английский

---

Single-cell RNA sequencing to identify cellular heterogeneity and targets in cardiovascular diseases: from bench to bedside

Basic Research in Cardiology, Journal Year: 2023, Volume and Issue: 118(1)

Published: Feb. 7, 2023

Language: Английский

---