Immunopharmacology of Post-Myocardial Infarction and Heart Failure Medications

The immune system responds to acute tissue damage after myocardial infarction (MI) and orchestrates healing and recovery of the heart. However, excessive inflammation may lead to additional tissue damage and fibrosis and exacerbate subsequent functional impairment, leading to heart failure. The appreciation of the immune system as a crucial factor after MI has led to a surge of clinical trials investigating the potential benefits of immunomodulatory agents previously used in hyper-inflammatory conditions, such as autoimmune disease. While the major goal of routine post-MI pharmacotherapy is to support heart function by ensuring appropriate blood pressure and cardiac output to meet the demands of the body, several drug classes also affect a range of immunological pathways and modulate the post-MI immune response, which is crucial to take into account when designing future immunomodulatory trials. This review outlines how routine post-MI pharmacotherapy affects the immune response and may thus influence post-MI outcomes and development towards heart failure. Current key drug classes are discussed, including platelet inhibitors, statins, β-blockers, and renin–angiotensin–aldosterone inhibitors.

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Multiple roles of cardiac macrophages in heart homeostasis and failure

Heart Failure Reviews ◽

10.1007/s10741-021-10156-z ◽

2021 ◽

Author(s):

Aneta Moskalik ◽

Justyna Niderla-Bielińska ◽

Anna Ratajska

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Steady State ◽

Immune System ◽

Cardiac Remodeling ◽

The Body ◽

Multiple Roles ◽

Normal Functioning ◽

Essential Components ◽

Arterial Tone

AbstractMacrophages are essential components of the immune system and play a role in the normal functioning of the cardiovascular system. Depending on their origin and phenotype, cardiac macrophages perform various functions. In a steady-state, these cells play a beneficial role in maintaining cardiac homeostasis by defending the body from pathogens and eliminating apoptotic cells, participating in electrical conduction, vessel patrolling, and arterial tone regulation. However, macrophages also take part in adverse cardiac remodeling that could lead to the development and progression of heart failure (HF) in such HF comorbidities as hypertension, obesity, diabetes, and myocardial infarction. Nevertheless, studies on detailed mechanisms of cardiac macrophage function are still in progress, and could enable potential therapeutic applications of these cells. This review aims to present the latest reports on the origin, heterogeneity, and functions of cardiac macrophages in the healthy heart and in cardiovascular diseases leading to HF. The potential therapeutic use of macrophages is also briefly discussed.

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The Mechanism of Stimulating and Mobilizing the Immune System Enhancing the Anti-Tumor Immunity

Frontiers in Immunology ◽

10.3389/fimmu.2021.682435 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zhengguo Wu ◽

Shang Li ◽

Xiao Zhu

Keyword(s):

Immune Response ◽

Immune System ◽

Tumor Microenvironment ◽

Cancer Immunotherapy ◽

Tumor Immunity ◽

Checkpoint Inhibitors ◽

The Body ◽

Research Progress ◽

Effective Population ◽

Cell Components

Cancer immunotherapy is a kind of therapy that can control and eliminate tumors by restarting and maintaining the tumor-immune cycle and restoring the body’s normal anti-tumor immune response. Although immunotherapy has great potential, it is currently only applicable to patients with certain types of tumors, such as melanoma, lung cancer, and cancer with high mutation load and microsatellite instability, and even in these types of tumors, immunotherapy is not effective for all patients. In order to enhance the effectiveness of tumor immunotherapy, this article reviews the research progress of tumor microenvironment immunotherapy, and studies the mechanism of stimulating and mobilizing immune system to enhance anti-tumor immunity. In this review, we focused on immunotherapy against tumor microenvironment (TME) and discussed the important research progress. TME is the environment for the survival and development of tumor cells, which is composed of cell components and non-cell components; immunotherapy for TME by stimulating or mobilizing the immune system of the body, enhancing the anti-tumor immunity. The checkpoint inhibitors can effectively block the inhibitory immunoregulation, indirectly strengthen the anti-tumor immune response and improve the effect of immunotherapy. We also found the checkpoint inhibitors have brought great changes to the treatment model of advanced tumors, but the clinical treatment results show great individual differences. Based on the close attention to the future development trend of immunotherapy, this study summarized the latest progress of immunotherapy and pointed out a new direction. To study the mechanism of stimulating and mobilizing the immune system to enhance anti-tumor immunity can provide new opportunities for cancer treatment, expand the clinical application scope and effective population of cancer immunotherapy, and improve the survival rate of cancer patients.

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Abstract 14482: Apparent Resistant Hypertension is a Marker of Risk: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽

10.1161/circ.142.suppl_3.14482 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Magnus O Wijkman ◽

Marcus Malachias ◽

Brian Claggett ◽

Susan Cheng ◽

Kunihiro Matsushita ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Antihypertensive Drug ◽

Resistant Hypertension ◽

Composite Endpoint ◽

Atherosclerosis Risk In Communities ◽

Drug Classes ◽

Atherosclerosis Risk ◽

Aric Study

Introduction: Apparent resistant hypertension (ARH) is a common marker of risk in patients with established cardiovascular disease. We ascertained the prevalence and prognostic significance of ARH in patients without prior cardiovascular disease. Methods: This prospective observational cohort study included 9669 community-based participants without a history of heart failure, myocardial infarction, or stroke, who completed the Atherosclerosis Risk in Communities (ARIC) study visit 4 between 1996-1998. The definition of ARH was blood pressure (BP) above goal (traditional goal <140/90mmHg, more stringent goal <130/80mmHg) despite use of ≥3 antihypertensive drug classes, or any BP with ≥4 antihypertensive drug classes. Participants with controlled hypertension (CH), defined as BP at goal with use of 1-3 antihypertensive drug classes, constituted the reference group. The outcome was a composite endpoint of heart failure, myocardial infarction, stroke, or death. Cox regression models were adjusted for age, sex, race, BMI, heart rate, smoking, eGFR, LDL, HDL, triglycerides, glucose, and diabetes. Results: Applying the traditional BP goal, 154/9669 participants (1.6%) had ARH, and there were 2311 participants with CH (23.9%). Using the more stringent BP goal, 218/9669 participants (2.3%) had ARH, and 1523 participants (15.8 %) had CH. The median follow-up time was 19 years. Apparent resistant hypertension was associated with an increased risk for the composite endpoint (adjusted hazard ratio 1.58 [95% CI 1.32-1.90] with the traditional BP goal, and adjusted hazard ratio 1.51 [95% CI 1.28-1.79] with the more stringent BP goal). Conclusions: Apparent resistant hypertension had a low prevalence but was independently associated with adverse outcome during long term follow-up, compared to controlled hypertension and even compared to uncontrolled hypertension. This was observed for both traditional and more stringent BP goals.

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Clinical Study of The Early Application of Lvabradine For Acute Anterior Myocardial Infarction Patients After PCI With Early Heart Failure To Observe Cardiac Function And Prognosis

10.21203/rs.3.rs-516241/v1 ◽

2021 ◽

Author(s):

Jun-Qing Gao ◽

Xu wang ◽

Ling-Yan Li ◽

Hua Zhang ◽

Hong Zhang ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Acute Myocardial Infarction ◽

Heart Function ◽

Coronary Intervention ◽

Left Ventricular ◽

Anterior Myocardial Infarction ◽

Standard Drug ◽

End Diastolic Volume ◽

Percutaneous Coronary

Abstract BackgroundThe incidence of acute myocardial infarction is increasing each year. Percutaneous coronary intervention has become highly preferred for patients with acute myocardial infarction because it not traumatic and improves heart function. However, the mortality and disability rates are still high. For the first time, we used ivabradine in patients with acute anterior myocardial infarction. We expect that this new method will enhance heart function and clinical prognosis because of heart rate control, decreases in heart preload and improvements in left ventricular end-diastolic volume.Method and analysisThis is a prospective, randomized, controlled, open-label, multicenter and optimally designed clinical trial. A total of 500 patients with acute anterior myocardial infarction after Percutaneous coronary intervention（PCI）with early heart failure will be enrolled. Eligible subjects will be randomized at a 1:1 ratio to take the standard drug treatment or receive the standard drug treatment plus ivabradine. The primary outcome measure is left ventricular end-diastolic volume. Left ventricular ejection fraction, adverse cardiac events, and the Canadian angina pectoris score will be evaluated as secondary endpoints. Blood biochemical testing will be used as the safety endpoints. Ethics and dissemination The clinical research will be carried out in strict accordance with the relevant Chinese laws and regulations, the Declaration of Helsinki, and the ethical and scientific principles stipulated by the Chinese GCP. All participants will provide informed consent. The personal information of patients will be kept confidential. Findings from the trial will be disseminated through peer-reviewed journals and scientific conferences.ClinicalTrials.govID:ChiCTR2000032731,Registered8May,2020 http://www.chictr.org.cn/showproj.aspx?proj=53275 Trial Statusversion number: Protocol version 1.0., approved9 May，2020Trial ongoingStudy execute time: From 1 September 2020 to 31 Octomber 2022Recruiting time: From 8 May 2020 to 31 December 2022

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MicroRNA-Related Strategies to Improve Cardiac Function in Heart Failure

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.773083 ◽

2021 ◽

Vol 8 ◽

Author(s):

Huatao Zhou ◽

Weijie Tang ◽

Jinfu Yang ◽

Jun Peng ◽

Jianjun Guo ◽

...

Keyword(s):

Heart Failure ◽

Heart Function ◽

The Body ◽

Chemical Modifications ◽

Non Coding Rna ◽

New Directions ◽

Future Challenges ◽

Flow Through ◽

Mirna Therapeutics ◽

Novel Therapeutic

Heart failure (HF) describes a group of manifestations caused by the failure of heart function as a pump that supports blood flow through the body. MicroRNAs (miRNAs), as one type of non-coding RNA molecule, have crucial roles in the etiology of HF. Accordingly, miRNAs related to HF may represent potential novel therapeutic targets. In this review, we first discuss the different roles of miRNAs in the development and diseases of the heart. We then outline commonly used miRNA chemical modifications and delivery systems. Further, we summarize the opportunities and challenges for HF-related miRNA therapeutics targets, and discuss the first clinical trial of an antisense drug (CDR132L) in patients with HF. Finally, we outline current and future challenges and potential new directions for miRNA-based therapeutics for HF.

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Considering Cause and Effect of Immune Cell Aging on Cardiac Repair after Myocardial Infarction

Cells ◽

10.3390/cells9081894 ◽

2020 ◽

Vol 9 (8) ◽

pp. 1894 ◽

Cited By ~ 1

Author(s):

Stephanie W. Tobin ◽

Faisal J. Alibhai ◽

Richard D. Weisel ◽

Ren-Ke Li

Keyword(s):

Myocardial Infarction ◽

Immune System ◽

Immune Cell ◽

Heart Function ◽

Cardiac Repair ◽

Cell Aging ◽

Cell Behavior ◽

Complex Nature ◽

Older Individuals ◽

Hematopoietic Stem

The importance of the immune system for cardiac repair following myocardial infarction is undeniable; however, the complex nature of immune cell behavior has limited the ability to develop effective therapeutics. This limitation highlights the need for a better understanding of the function of each immune cell population during the inflammatory and resolution phases of cardiac repair. The development of reliable therapies is further complicated by aging, which is associated with a decline in cell and organ function and the onset of cardiovascular and immunological diseases. Aging of the immune system has important consequences on heart function as both chronic cardiac inflammation and an impaired immune response to cardiac injury are observed in older individuals. Several studies have suggested that rejuvenating the aged immune system may be a valid therapeutic candidate to prevent or treat heart disease. Here, we review the basic patterns of immune cell behavior after myocardial infarction and discuss the autonomous and nonautonomous manners of hematopoietic stem cell and immune cell aging. Lastly, we identify prospective therapies that may rejuvenate the aged immune system to improve heart function such as anti-inflammatory and senolytic therapies, bone marrow transplant, niche remodeling and regulation of immune cell differentiation.

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Biomechanical assessment of remote and postinfarction scar remodeling following myocardial infarction

Scientific Reports ◽

10.1038/s41598-019-53351-7 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Mihaela Rusu ◽

Katrin Hilse ◽

Alexander Schuh ◽

Lukas Martin ◽

Ioana Slabu ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Type I Collagen ◽

De Novo ◽

Heart Function ◽

Type Iii Collagen ◽

Type I ◽

Compensatory Mechanisms ◽

Biomechanical Assessment ◽

Type V

AbstractThe importance of collagen remodeling following myocardial infarction (MI) is extensively investigated, but little is known on the biomechanical impact of fibrillar collagen on left ventricle post-MI. We aim to identify the significant effects of the biomechanics of types I, III, and V collagen on physio-pathological changes of murine hearts leading to heart failure. Immediately post-MI, heart reduces its function (EF = 40.94 ± 2.12%) while sarcomeres’ dimensions are unchanged. Strikingly, as determined by immunohistochemistry staining, type V collagen fraction significantly grows in remote and scar for sustaining de novo-types I and III collagen fibers’ assembly while hindering their enzymatic degradation. Thereafter, the compensatory heart function (EF = 63.04 ± 3.16%) associates with steady development of types I and III collagen in a stiff remote (12.79 ± 1.09 MPa) and scar (22.40 ± 1.08 MPa). In remote, the soft de novo-type III collagen uncoils preventing further expansion of elongated sarcomeres (2.7 ± 0.3 mm). Once the compensatory mechanisms are surpassed, the increased turnover of stiff type I collagen (>50%) lead to a pseudo-stable biomechanical regime of the heart (≅9 MPa) with reduced EF (50.55 ± 3.25%). These end-characteristics represent the common scenario evidenced in patients suffering from heart failure after MI. Our pre-clinical data advances the understanding of the cause of heart failure induced in patients with extended MI.

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Plant Phenolics and Lectins as Vaccine Adjuvants

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666190716110705 ◽

2019 ◽

Vol 20 (15) ◽

pp. 1236-1243 ◽

Cited By ~ 2

Author(s):

Hernández-Ramos Reyna-Margarita ◽

Castillo-Maldonado Irais ◽

Rivera-Guillén Mario-Alberto ◽

Ramírez-Moreno Agustina ◽

Serrano-Gallardo Luis-Benjamín ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Innate Immune Response ◽

Adaptive Immune Response ◽

The Body ◽

Innate Immune ◽

Vaccine Adjuvants ◽

Plant Phenolics ◽

Adaptive Immune ◽

Foreign Substance

Background: The immune system is responsible for providing protection to the body against foreign substances. The immune system divides into two types of immune responses to study its mechanisms of protection: 1) Innate and 2) Adaptive. The innate immune response represents the first protective barrier of the organism that also works as a regulator of the adaptive immune response, if evaded the mechanisms of the innate immune response by the foreign substance the adaptive immune response takes action with the consequent antigen neutralization or elimination. The adaptive immune response objective is developing a specific humoral response that consists in the production of soluble proteins known as antibodies capable of specifically recognizing the foreign agent; such protective mechanism is induced artificially through an immunization or vaccination. Unfortunately, the immunogenicity of the antigens is an intrinsic characteristic of the same antigen dependent on several factors. Conclusion: Vaccine adjuvants are chemical substances of very varied structure that seek to improve the immunogenicity of antigens. The main four types of adjuvants under investigation are the following: 1) Oil emulsions with an antigen in solution, 2) Pattern recognition receptors activating molecules, 3) Inflammatory stimulatory molecules or activators of the inflammasome complex, and 4) Cytokines. However, this paper addresses the biological plausibility of two phytochemical compounds as vaccine adjuvants: 5) Lectins, and 6) Plant phenolics whose characteristics, mechanisms of action and disadvantages are addressed. Finally, the immunological usefulness of these molecules is discussed through immunological data to estimate effects of plant phenolics and lectins as vaccine adjuvants, and current studies that have implanted these molecules as vaccine adjuvants, demonstrating the results of this immunization.

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Immunological changes accompanying the development of experimental neoplastic process

Pediatrician (St Petersburg) ◽

10.17816/ped6296-108 ◽

2015 ◽

Vol 6 (2) ◽

pp. 96-108

Author(s):

Elena Aleksandrovna Dementeva ◽

Olga Petrovna Gurina

Keyword(s):

Immune Response ◽

Immune System ◽

Genome Stability ◽

Cell Types ◽

Transformation Process ◽

The Body ◽

Expression Of Genes ◽

Neoplastic Process ◽

And Control ◽

Different Cell Types

The key immunology problem remains the understanding of the mechanisms for the effective protection of the body against various pathogens with simultaneous suppression of the immune response to autoantigens. The pathogenesis of neoplastic pathological processes includes violations of the mechanisms of normal cell growth and cell proliferation. Antitumor immune response is a complex event, involving many different cell types. But despite the ability of the immune system to recognize and respond to a variety of tumor-associated antigens, the neoplastic process overcomes the protective forces of the organism, grows and spreads. For cancer cells characterized by independence from antiproliferative signals, autocrine stimulation of growth disturbances in the system, induction of apoptosis and control of genome stability. As a result of accumulation of genetic and epigenetic changes in tumor cells differ significantly from the normal range and the level of expression of genes involved in the transformation process, the accumulation of mutations in key genes promoters and suppressors of tumorigenesis. This creates the opportunity for recognition by cells of the immune system. The study of changes in value and operation of the various elements of the immune system in the development of experimental neoplastic process allows you to identify the mechanisms of interaction in the system «malignant tumor-immune system, to assess patterns of interaction with other organs and tissues, to create a theoretical pathogenetically reasonable premise for the development of anticancer therapy.

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Yolkin Isolated from Hen Egg Yolk as a Natural Immunoregulator, Activating Innate Immune Response in BMDM Macrophages

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/5731021 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

W. Kazana ◽

M. Mitkiewicz ◽

M. Ochnik ◽

M. Sochocka ◽

A. Zambrowicz ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Innate Immune Response ◽

Egg Yolk ◽

The Body ◽

Innate Immune ◽

Type I ◽

Dependent Manner ◽

Hen Egg Yolk ◽

Hen Egg

One of the goals of biomedical sciences is to search and identify natural compounds that are safe, have no side effects, and possess immunostimulatory activity. It has been proven that medicines of natural origin can be effective agents, supporting the therapy of many diseases, not only in the weakened immune system of the body but also in the prevention of many diseases in healthy people. It has been shown that yolkin, a polypeptide complex isolated from hen egg yolk as a fraction accompanying immunoglobulin Y (IgY), possesses potential biological activity. However, the mechanism of its action has not been explained. The objective of this investigation was to examine the molecular mechanisms of innate immune response, activated in response to yolkin, in murine bone marrow-derived macrophages (BMDM). It was shown that yolkin induced phosphorylation of extracellular signal-kinases (ERK1/2) and c-Jun N-terminal kinase (JNK) and upregulated expression and production of type I interferons, TNF-α (tumor necrosis factor α), and nitric oxide (NO), in BMDM cells. Using pharmacological inhibitors of ERK 1/2 and JNK kinases, we revealed that the JNK signaling cascade is required for yolkin-induced inducible NOS expression and upregulation of NO production in mouse macrophages. Using the TLR4-deficient BMDM cell line, we established that yolkin can activate macrophages in a TLR4-dependent manner. It was also shown that NO, TNF-α, and type I IFNs (α/β) produced by BMDM cells in response to yolkin triggered antiviral activity. These data indicate that yolkin affects the regulation of the immune system and antiviral response; therefore, it can be used as an effective immunostimulator of the innate immunity or as a supplement of the conventional therapy of immunodeficiency.

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