scholarly journals Single-cell Transcriptome Analysis Indicates New Potential Regulation Mechanism of ACE2 and NPs signaling among heart failure patients infected with SARS-CoV-2

2020 ◽  
Author(s):  
Dachun Xu ◽  
Mengqiu Ma ◽  
Yanhua Xu ◽  
Yang Su ◽  
Sang-Bing Ong ◽  
...  
Keyword(s):  
Heart Failure ◽  
Single Cell ◽  
Natriuretic Peptides ◽  
Cardiac Dysfunction ◽  
Feedback Loop ◽  
Gene Expression Pattern ◽  
Case Series ◽  
Regulation Mechanism ◽  
High Morbidity ◽  
Protective Effects

AbstractThe coronavirus disease 2019 (COVID-19) has resulted in high morbidity and mortality worldwide since December 2019. Recent studies showed that patients with previous heart disease, especially heart failure (HF), whose plasma Natriuretic Peptides (NPs) concentrations are higher, were more susceptible to SARS-CoV-2 infection. In this study, we retrospectively analyzed single-center case series of 91 patients with COVID-19 in China. 46 (50.5%) patients exhibited cardiac dysfunction as indicated by elevated Natriuretic Peptides B (BNP) levels. Moreover, the results indicate that patients with cardiac dysfunction had higher mortality than those without cardiac dysfunction. Nonetheless, it remains unclear as to how the virus infects the heart, especially in HF patients and why a higher level of BNP in the heart dampen inflammation. Angiotensin-converting enzyme 2 (ACE2), the critical host cellular receptor of SARS-CoV-2, expresses in different organs. Still, its cellular distribution in the human heart, especially in patients with HF remains unclear. Thus, we investigated ACE2 gene expression pattern in single-cell RNA sequence (scRNA-seq) data of hearts from normal adults versus patients with HF. Our results indicate that ACE2 is predominantly enriched in cardiomyocytes (CMs), endothelial cells, fibroblasts and smooth muscle cells in normal heart. Not only ACE2+ CMs, but also expression of ACE2 are significantly boosted in CMs of patients with HF. Also, genes related to virus entry, virus replication and suppression of IFN-γ signaling besides ACE2 were up-regulated in HF patient, mainly in CMs, indicating the higher susceptibility to SARS-CoV-2 infection. Interestingly, NPs are significantly up-regulated in ACE2-postive (ACE2+) ventricular myocytes and share the upstream transcription factor. ACE2 and NPs can form a negative feedback loop with protective effects. But it maybe turns into a positive feedback loop by virus and ineffective NPs, which lead to severe prognosis. In summary, the increased expression of ACE2, NPs during HF predisposes to SARS-CoV-2 infection. Modulating the levels of ACE2, NPs therefore may potentially be a novel therapeutic target to prevent the SARS-CoV-2 infection.

CLINICAL USE OF NATRIURETIC PEPTIDES. A REVIEW

2008 ◽  
Vol 37 (2) ◽  
pp. 174-179
Author(s):  
Mugdim Bajric ◽  
Fahir Barakovic ◽  
Nusret Sinanovic ◽  
Denis Mrsic
Keyword(s):  
Heart Failure ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Vascular Wall ◽  
Clinical Use ◽  
Protective Effects ◽  
Special Effect ◽  
Early Evaluation ◽  
Hemodynamic Processes

The most significant discoveries in the area of heart failure are the recognition of natriuretic peptide system and its multiple effects on cardiac structure and function with special effect on its natriuretic and hemodynamic processes. First information’s that heart, beside its function as a mechanical pump also has an important endocrine functions, exists for over 50 years. Chemical structure of atrial natriuretic peptide has been identified in 1984. and four years later a brain natriuretic peptide has been discovered owning its name because it has been identified in pig brain. Primary site of brain natriuretic peptide synthesis in heart has been identified in 1991. Natriuretic peptides are neither neurohormones that influence body fluid homeostasis through natriuretic and diuretic effect; regulate vascular tone by decreasing angiotensine II level and they inhibit nor epinephrine synthesis and increase parasympathetic tone. They are natural antagonists of renin-angiotensine-aldosteron system, and they have a great role in inhibition of ventricular hypertrophy and remodeling, protective effects in endothelial dysfunction are important; they increase effects of nitrite oxide, inhibit lipid deposition in vascular wall and inhibit thrombocyte activation, regulate coagulation and fibrinolytic processes as well. Natriuretic peptides clinical use is in early evaluation of heart failure, prognostic stratification and detection of systolic and diastolic dysfunction of left ventricle, assessment of prognosis during patient monitoring period, differential diagnosis of dyspnea, treatment adjustment and dosage titration, assessment during hospital admittance and discharge and forecast and reduction of coronary events.

scholarly journals Atrial and Brain Natriuretic Peptides- Benefits and Limits of their use in Cardiovascular Diseases

2019 ◽  
Vol 15 (4) ◽  
pp. 283-290
Author(s):  
Mustafa Edme Roxana ◽  
TÃrtea Georgică ◽  
Donoiu Ionuț ◽  
Moise Gianina ◽  
Florescu Cristina
Keyword(s):  
Heart Failure ◽  
Natriuretic Peptides ◽  
Cardiac Dysfunction ◽  
Intravascular Volume ◽  
Threshold Values ◽  
Beneficial Effects ◽  
Diagnosis And Prognosis ◽  
Brain Natriuretic Peptides ◽  
Clinical Benefits ◽  
Neuroendocrine Activation

Natriuretic peptides, produced by cardiac myocytes, are regulators of the intravascular volume and blood pressure, and also exhibit neuroendocrine, metabolic and growth controlling effects. In heart failure, their synthesis increases exponentially as part of the neuroendocrine activation, but their beneficial effects are diminished. The paper reviews relevant data about their role as diagnosis and prognosis markers in heart failure, the hemodynamic and clinical benefits of their use as therapy in heart failure, together with the main adverse effects. Peptides non-specifically increase in extracardiac pathology and the literature reveals the mechanisms of increase, significance and threshold values to exclude cardiac dysfunction.

The use of levosimendan in children with cancer with severe acute cardiac dysfunction: case series and a review of the literature

2013 ◽  
Vol 24 (3) ◽  
pp. 524-527 ◽  
Author(s):  
Alvise Tosoni ◽  
Anne I. Dipchand ◽  
Hadi Mohseni-Bod
Keyword(s):  
Heart Failure ◽  
Bone Marrow ◽  
Cardiac Dysfunction ◽  
Case Series ◽  
Marrow Transplant ◽  
Loading Dose ◽  
Review Of The Literature ◽  
Heart Failure Therapy ◽  
Children With Cancer ◽  
Initial Management

AbstractWe report the use of levosimendan in two febrile, neutropenic children with cancer – one post bone marrow transplant – with acute heart failure following chemotherapy. Initial management with epinephrine, milrinone, and diuresis was unsuccessful. Infusion of levosimendan without a loading dose was added to the ongoing heart failure therapy, which resulted in persistent symptomatic and echocardiographic improvement without major side effects.

scholarly journals Single-Cell Transcriptome Analysis Decipher New Potential Regulation Mechanism of ACE2 and NPs Signaling Among Heart Failure Patients Infected With SARS-CoV-2

2021 ◽  
Vol 8 ◽  
Author(s):  
Mengqiu Ma ◽  
Yanhua Xu ◽  
Yang Su ◽  
Sang-Bing Ong ◽  
Xingdong Hu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Virus Infection ◽  
Single Cell ◽  
Clinical Outcomes ◽  
Virus Entry ◽  
Underlying Mechanism ◽  
Organ Injury ◽  
Regulation Mechanism ◽  
Increased Risk ◽  
Cell Transcriptome

Aims: COVID-19 patients with comorbidities such as hypertension or heart failure (HF) are associated with poor clinical outcomes. The cellular distribution of Angiotensin-converting enzyme 2 (ACE2), the critical enzyme for SARS-CoV-2 infection, in the human heart is unknown. We explore the underlying mechanism that leads to increased susceptibility to SARS-CoV-2 in patients with cardiovascular diseases and patients of cardiac dysfunction have increased risk of multi-organ injury compared with patients of normal cardiac function.Methods and Results: We analyzed single-cell RNA sequencing (scRNA-seq) data in both normal and failing hearts. The results demonstrated that ACE2 is present in cardiomyocytes (CMs) and non-CMs, while the number of ACE2-postive (ACE2+) CMs and ACE2 gene expression in these CMs are significantly increased in the failing hearts. Interestingly, both brain natriuretic peptides (BNP) and atrial natriuretic peptide (ANP) are significantly up-regulated in the ACE2+ CMs, which is consistent with other studies that ACE2, ANP, and BNP increased in HF patients. We found that genes related to virus entry, virus replication and suppression of interferon-gamma signaling are all up-regulated in failing CMs, and the increase was significantly higher in ACE2+ CMs, suggesting that these CMs may be more vulnerable to virus infection. As the level of expression of both ACE2 and BNP in CMs were up-regulated, we further performed retrospective analysis of the plasma BNP levels and clinical outcomes of 91 COVID-19 patients from a single-center. Patients with higher plasma BNP were associated with significantly higher mortality and expression levels of inflammatory and infective markers.Conclusion: In the failing heart, the upregulation of ACE2 and virus infection associated genes could potentially facilitate SARS-CoV-2 virus entry and replication in these vulnerable cardiomyocyte subsets. COVID-19 patients with higher plasma BNP levels had poorer clinical outcomes. These observations may allude to a potential regulatory association between ACE2 and BNP in mediating myocarditis associated with COVID-19.

scholarly journals Adenosine regulation of microtubule dynamics in cardiac hypertrophy

2009 ◽  
Vol 297 (2) ◽  
pp. H523-H532 ◽  
Author(s):  
John T. Fassett ◽  
Xin Xu ◽  
Xinli Hu ◽  
Guangshuo Zhu ◽  
Joel French ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Knockout Mice ◽  
Cardiac Dysfunction ◽  
Pressure Overload ◽  
Colchicine Treatment ◽  
Microtubule Dynamics ◽  
Protective Effects ◽  
Wild Type ◽  
Extracellular Adenosine

There is evidence that endogenous extracellular adenosine reduces cardiac hypertrophy and heart failure in mice subjected to chronic pressure overload, but the mechanism by which adenosine exerts these protective effects is unknown. Here, we identified a novel role for adenosine in regulation of the cardiac microtubule cytoskeleton that may contribute to its beneficial effects in the overloaded heart. In neonatal cardiomyocytes, phenylephrine promoted hypertrophy and reorganization of the cytoskeleton, which included accumulation of sarcomeric proteins, microtubules, and desmin. Treatment with adenosine or the stable adenosine analog 2-chloroadenosine, which decreased hypertrophy, specifically reduced accumulation of microtubules. In hypertrophied cardiomyocytes, 2-chloroadenosine or adenosine treatment preferentially targeted stabilized microtubules (containing detyrosinated α-tubulin). Consistent with a role for endogenous adenosine in reducing microtubule stability, levels of detyrosinated microtubules were elevated in hearts of CD73 knockout mice (deficient in extracellular adenosine production) compared with wild-type mice (195%, P < 0.05). In response to aortic banding, microtubules increased in hearts of wild-type mice; this increase was exaggerated in CD73 knockout mice, with significantly greater amounts of tubulin partitioning into the cold-stable Triton-insoluble fractions. The levels of this stable cytoskeletal fraction of tubulin correlated strongly with the degree of heart failure. In agreement with a role for microtubule stabilization in promoting cardiac dysfunction, colchicine treatment of aortic-banded mice reduced hypertrophy and improved cardiac function compared with saline-treated controls. These results indicate that microtubules contribute to cardiac dysfunction and identify, for the first time, a role for adenosine in regulating cardiomyocyte microtubule dynamics.

Natriuretic Peptides – Addressing the Dilemma of Heart Failure Management

2011 ◽  
Vol 7 (2) ◽  
pp. 104
Author(s):  
Kenneth McDonald ◽  
Ulf Dahlström ◽  
◽  
Keyword(s):  
Heart Failure ◽  
Physical Examination ◽  
Natriuretic Peptides ◽  
Normal Values ◽  
Outpatient Setting ◽  
Heart Failure Management ◽  
Effective Screening ◽  
Specific Symptoms ◽  
Objective Marker

Heart failure (HF) is characterised by non-specific symptoms and unremarkable physical examination; therefore, the need exists for an available objective marker of HF status. Natriuretic peptides (NPs) are a marker that can aid the dilemmas in present-day HF management. More effective screening for clinical deterioration would include changes in brain natriuretic peptide (BNP) levels. Normal values for BNP, <50–100 pg/ml, have excellent negative predictive value (NPV) in excluding HF as a diagnosis. BNP values that are significantly elevated, e.g. >500 pg/ml, make the diagnosis of HF more likely. There are now established and emerging uses for NPs in managing HF in the community. These include the role of NPs at the time of possible new presentation of HF, its role in prognostication and, finally, the increasing interest in using NPs to guide therapy in the outpatient setting.

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