scholarly journals New Insights into Mechanisms of Cardioprotection Mediated by Thyroid Hormones

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
G. Nicolini ◽  
L. Pitto ◽  
C. Kusmic ◽  
S. Balzan ◽  
L. Sabatino ◽  
...  
Keyword(s):  
Heart Failure ◽  
Thyroid Hormone ◽  
Cardiac Remodeling ◽  
Regulatory Networks ◽  
Cardiac Tissue ◽  
Experimental Models ◽  
Hormone Regulation ◽  
Chronic Heart Disease ◽  
Cardiac Mitochondrion

Heart failure represents the final common outcome in cardiovascular diseases. Despite significant therapeutic advances, morbidity and mortality of heart failure remain unacceptably high. Heart failure is preceded and sustained by a process of structural remodeling of the entire cardiac tissue architecture. Prevention or limitation of cardiac remodeling in the early stages of the process is a crucial step in order to ameliorate patient prognosis. Acquisition of novel pathophysiological mechanisms of cardiac remodeling is therefore required to develop more efficacious therapeutic strategies. Among all neuroendocrine systems, thyroid hormone seems to play a major homeostatic role in cardiovascular system. In these years, accumulating evidence shows that the “low triiodothyronine” syndrome is a strong prognostic, independent predictor of death in patients affected by both acute and chronic heart disease. In experimental models of cardiac hypertrophy or myocardial infarction, alterations in the thyroid hormone signaling, concerning cardiac mitochondrion, cardiac interstitium, and vasculature, have been suggested to be related to heart dysfunction. The aim of this brief paper is to highlight new developments in understanding the cardioprotective role of thyroid hormone in reverting regulatory networks involved in adverse cardiac remodeling. Furthermore, new recent advances on the role of specific miRNAs in thyroid hormone regulation at mitochondrion and interstitial level are also discussed.

scholarly journals The role of the cardiac lymphatic system in the development and progression of heart failure and novel therapeutic approaches for its management in post-infarction cardiac remodeling

2020 ◽  
Vol 19 (3) ◽  
pp. 2281
Author(s):  
Yu. S. Korneva ◽  
R. V. Ukrainets
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Remodeling ◽  
Lymphatic Vessels ◽  
Myocardial Damage ◽  
Myocardial Edema ◽  
Experimental Models ◽  
Vital Role ◽  
Treatment Regimens

Cardiac lymphatic vessels play a vital role in maintaining homeostasis in both physiological and pathological conditions, providing outflow of metabolites. It has been shown that myocardial infarction and postinfarction cardiac remodeling is accompanied by the lymphatic remodeling, which entails functional disorders and is of great importance in heart failure pathogenesis. As a result of progressive myocardial edema, hypoxia and fibrosis of the interstitial space increase, aggravating edema. Other pathways of additional myocardial damage and contractility reduction are triggered. Lymphatic efflux is associated with arrhythmias. Experimental models showed the positive effect of exogenous activation of lymphangiogenesis in relation to the prevention and treatment of heart failure, which can be further used to improve treatment regimens. This review discusses cardiac lymphatic remodeling after myocardial infarction, as well as the pathogenesis of related complications.

New insights into the role of thyroid hormone in cardiac remodeling: time to reconsider?

2010 ◽  
Vol 16 (1) ◽  
pp. 79-96 ◽  
Author(s):  
Constantinos Pantos ◽  
Iordanis Mourouzis ◽  
Dennis V. Cokkinos
Keyword(s):  
Thyroid Hormone ◽  
Cardiac Remodeling

Abstract 354: The Role of the Liver Heart Axis During Cardiac Remodeling

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Soichiro Usui ◽  
Shin-ichiro Takashima ◽  
Kenji Sakata ◽  
Masa-aki Kawashiri ◽  
Masayuki Takamura
Keyword(s):  
Heart Failure ◽  
Insulin Resistance ◽  
Cardiac Remodeling ◽  
Pressure Overload ◽  
Normal Subjects ◽  
Serum Levels ◽  
Lung Weight ◽  
Reduced Ejection Fraction ◽  
Hepatic Expression

Background: Hepatokine selenoprotein P (SeP) contributes to insulin resistance and hyperglycemia in patients with type 2 diabetes. Although clinical studies suggest the insulin resistance is an independent risk factor of heart failure and inhibition of SeP protects the heart from ischemia reperfusion injury, the role of SeP in pathogenesis of chronic heart failure is not well understood. Objective: We examined the role of SeP in the regulation of cardiac remodeling in response to pressure overload. Methods and Results: We measured serum SeP levels in 22 patients for heart failure with reduced ejection fraction (HFrEF; LVEF<50%) and 22 normal subjects. Serum levels of SeP were significantly elevated in patients with HFrEF compared to in normal subjects (3.55 ± 0.43 vs 2.98 ± 0.43, p<0.01). To examine the role of SeP in cardiac remodeling, SeP knockout (KO) and wild-type (WT) mice were subjected to pressure overload (transverse aortic constriction (TAC)) for 2 weeks. The mortality rate following TAC was significantly decreased in SeP KO mice compared to WT mice (22.5 % in KO mice (n=40) vs 52.3 % in WT mice (n=39) p<0.01). LV weight/tibial length (TL) was significantly smaller in SeP KO mice than in WT mice (6.75 ± 0.24 vs 8.33 ± 0.32, p<0.01). Lung weight/TL was significantly smaller in SeP KO than in WT mice (10.46 ± 0.44 vs 16.38 ± 1.12, p<0.05). Interestingly, hepatic expression of SeP in WT was significantly increased by TAC. To determine whether hepatic overexpression of SeP affects TAC-induced cardiac hypertrophy, a hydrodynamic injection method was used to generate mice that overexpress SeP mRNA in the liver. Hepatic overexpression of SeP in SeP KO mice lead to a significant increase in LV weight/TL and Lung weight/TL after TAC compared to that in other SeP KO mice. Conclusions: These results suggest that serum levels of SeP were elevated in patients with heart failure with reduced ejection fraction and cardiac pressure overload induced hepatic expression of SeP in mice model. Gene deletion of SeP attenuated cardiac hypertrophy and dysfunction in response to pressure overload in mice. SeP possibly plays a pivotal role in promoting cardiac remodeling through the liver-heart axis.

scholarly journals The Emerging Role of MicroRNAs in Cardiac Remodeling and Heart Failure

2008 ◽  
Vol 103 (10) ◽  
pp. 1072-1083 ◽  
Author(s):  
Vijay Divakaran ◽  
Douglas L. Mann
Keyword(s):  
Heart Failure ◽  
Cardiac Remodeling

scholarly journals The Oxidative Stress and Chronic Inflammatory Process in Chagas Disease: Role of Exosomes and Contributing Genetic Factors

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Edio Maldonado ◽  
Diego A. Rojas ◽  
Fabiola Urbina ◽  
Aldo Solari
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Heart Failure ◽  
Immune Response ◽  
Chronic Inflammation ◽  
Chagas Disease ◽  
Genetic Factors ◽  
Cardiac Tissue ◽  
Chronic Phase

Chagas disease is a neglected tropical disease caused by the flagellated protozoa Trypanosoma cruzi that affects several million people mainly in Latin American countries. Chagas disease has two phases, which are acute and chronic, both separated by an indeterminate time period in which the infected individual is relatively asymptomatic. The acute phase extends for 40-60 days with atypical and mild symptoms; however, about 30% of the infected patients will develop a symptomatic chronic phase, which is characterized by either cardiac, digestive, neurological, or endocrine problems. Cardiomyopathy is the most important and severe result of Chagas disease, which leads to left ventricular systolic dysfunction, heart failure, and sudden cardiac death. Most deaths are due to heart failure (70%) and sudden death (30%) resulting from cardiomyopathy. During the chronic phase, T. cruzi-infected macrophages respond with the production of proinflammatory cytokines and production of superoxide and nitric oxide by the NADPH oxidase 2 (NOX2) and inducible nitric oxide synthase (iNOS) enzymes, respectively. During the chronic phase, myocardial changes are produced as a result of chronic inflammation, oxidative stress, fibrosis, and cell death. The cellular inflammatory response is mainly the result of activation of the NF-κB-dependent pathway, which activates gene expression of inflammatory cytokines, leading to progressive tissue damage. The persisting production of reactive oxygen species (ROS) is the result of mitochondrial dysfunction in the cardiomyocytes. In this review, we will discuss inflammation and oxidative damage which is produced in the heart during the chronic phase of Chagas disease and recent evidence on the role of macrophages and the production of proinflammatory cytokines during the acute phase and the origin of macrophages/monocytes during the chronic phase of Chagas disease. We will also discuss the contributing factors and mechanisms leading to the chronic inflammation of the cardiac tissue during the chronic phase of the disease as well as the innate and adaptive host immune response. The contribution of genetic factors to the progression of the chronic inflammatory cardiomyopathy of chronic Chagas disease is also discussed. The secreted extracellular vesicles (exosomes) produced for both T. cruzi and infected host cells can play key roles in the host immune response, and those roles are described. Lastly, we describe potential treatments to attenuate the chronic inflammation of the cardiac tissue, designed to improve heart function in chagasic patients.

scholarly journals Cardiac Tissue Factor Regulates Inflammation, Hypertrophy and Heart Failure in Mouse Model of Type 1 Diabetes

2021 ◽  
Author(s):  
Dasan Mary Cibi ◽  
Reddemma Sandireddy ◽  
Hanumakumar Bogireddy ◽  
Nicole Tee ◽  
Siti Aishah Binte Abdul Ghani ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Tissue Factor ◽  
Cardiac Tissue ◽  
Immune Cell ◽  
Preserved Ejection Fraction ◽  
Cardiac Inflammation ◽  
Protein Levels ◽  
Increased Risk

Diabetes patients have an increased risk of heart failure (HF). Diabetes is highly prevalent in HF with preserved ejection fraction (HFpEF), which is on the rise worldwide. The role of diabetes in HF is less established and available treatments of HF are not effective in HFpEF patients. Tissue factor (TF), a transmembrane receptor, plays an important role in immune-cell inflammation and atherothrombosis in diabetes. However, its role in diabetes-induced cardiac inflammation, hypertrophy, and HF has not been studied. Here, we have utilized Wildtype (WT), heterozygous, and Low-TF (with 1% human TF) mice to determine TF’s role in <i>Type1 diabetes</i>-induced HF. We found significant upregulation of cardiac TF mRNA and protein levels in diabetic WT hearts compared to non-diabetic controls. WT diabetic hearts also exhibited increased inflammation and cardiac hypertrophy versus controls. However, these changes in cardiac inflammation and hypertrophy were not found in diabetic Low-TF mice compared to their non-diabetic controls. TF deficiency was also associated with improved cardiac function parameters suggestive of HFpEF, which was evident in diabetic WT mice. The TF regulation of inflammation and cardiac remodeling was further dependent on downstream ERK1/2 and STAT3 pathways. In summary, our study demonstrated an important role of TF in regulating diabetes-induced inflammation, hypertrophy, and remodeling of the heart leading to HF with preserved ejection fraction.

Abstract 1271: IKKβ/NF-κB Pathway Protects Hearts from Hemodynamic Stress Mediated through Regulating MnSOD Expression

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Shungo Hikoso ◽  
Kinya Otsu ◽  
Osamu Yamaguchi ◽  
Toshihiro Takeda ◽  
Masayuki Taniike ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Cardiac Remodeling ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Negative Regulator ◽  
Iκb Kinase ◽  
Jnk Activation

Objectives: We have previously reported that NF-κB contributes to GPCR agonist-induced hypertrophy in cultured cardiomyocytes. However, the in vivo role of this pathway in the pathogenesis of cardiac remodeling remains to be elucidated. Although IκB kinase β (IKKβ)/NF-κB pathway is a major negative regulator of cell death, it can sensitize cells to death-inducing stimuli in some instances, thus it can be either anti- or pro-apoptotic. In this study, we aimed to clarify the role of IKKβ/NF-κB signaling in cardiac remodeling using cardiac-specific IKKβ deficient mice. Methods and Results: We crossed mice bearing an IKK β flox allele with mice expressing the Cre recombinase under the control of the myosin light chain 2v promoter ( MLC2v-Cre +/− ) to generate IKK β flox/flox ; MLC2v-Cre +/− mice (conditional knockout:CKO). Then, CKO mice (n=14) and control littermates bearing IKK β flox/flox (CTRL, n=14) were subjected to pressure overload by means of transverse aortic constriction (TAC). EMSA analysis revealed NF-κB DNA binding activity after TAC had attenuated in CKO hearts. One week after TAC, echocardiography showed significantly lower left ventricular fractional shortening (26.9±2.7% vs. 41.4±0.9%, p<0.01), and higher left ventricular end-diastolic dimension (4.02±0.14 mm vs. 3.47±0.08 mm, p<0.01) and lung weight/body weight ratio (11.1±1.4 vs. 5.5±0.1, p<0.01) in CKO mice compared with CTRL mice, indicating the development of heart failure in CKO mice. Number of apoptotic cells had increased in CKO hearts after TAC, suggesting that the enhanced apoptosis is a cause for heart failure. The expression levels of MnSOD mRNA and protein after TAC, which is one of NF-κB target genes, were significantly lower in CKO than those in CTRL mice. As a consequence, oxidative stress and JNK activation in CKO hearts after TAC had significantly increased compared with those in CTRL heart, suggesting that increased oxidative stress and enhanced JNK activity resulted in cardiomyocyte apoptosis in CKO hearts. Conclusion: These results show that IKKβ/NF-κB pathway in cardiomyocyte plays a protective role mediated through attenuation of oxidative stress and JNK activation in response to pressure overload.

Prospects for the use of thyroid hormones in patients with heart failure

2021 ◽  
Author(s):  
S. M. Pyvоvar ◽  
Yu. S. Rudyk ◽  
О. B. Krоtоva ◽  
L. V. Panina
Keyword(s):  
Heart Failure ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Animal Studies ◽  
Cardiac Tissue ◽  
Contractile Function ◽  
Heart Function ◽  
Experimental Studies ◽  
Tissue Level ◽  
Free Triiodothyronine

Thyroid hormone therapy in the setting of heart failure is still an «open book» today. There are several unanswered questions: the regimen, doses and schedule of the use of thyroid hormones, the consequences of such therapy. At the same time, the presence of a comorbid pathology of the thyroid gland, which requires the appointment of levothyroxine, allows one to partially answer these questions. Thyroid hormones affect the diastolic and systolic functions of the myocardium. Ventricular contractile function is also affected by changes in hemodynamic conditions secondary to thyroid hormones and peripheral vascular tone. Thyroid hormone homeostasis maintains a positive ventricular-arterial ratio, resulting in a favorable balance for heart function. Experimental studies in rats have shown that chronic hypothyroidism alone can eventually lead to heart failure. Other studies suggest a decrease in the level of free triiodothyronine in the myocardium after myocardial infarction or with arterial hypertension due to the activation of type 3 deiodinase, which leads to deactivation of triiodothyronine and thyroxine. To address these issues, the researchers propose conducting multicenter, randomized, placebo-controlled trials to evaluate the effects of thyroxine replacement in patients with chronic heart failure. The review highlights the growing body of evidence from animal studies and small clinical trials that suggests that low thyroid activity at the cardiac tissue level can negatively affect the progression of heart failure and that treatment with thyroid hormones can lead to an improved prognosis.

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