scholarly journals Common and Distinctive Intercellular Communication Patterns in Human Obstructive and Nonobstructive Hypertrophic Cardiomyopathy

2022 ◽  
Vol 23 (2) ◽  
pp. 946
Author(s):  
Christina J. Codden ◽  
Michael T. Chin
Keyword(s):  
Extracellular Matrix ◽  
Hypertrophic Cardiomyopathy ◽  
Dendritic Cell ◽  
Differentially Expressed Genes ◽  
Intercellular Communication ◽  
Cell Communication ◽  
Cell Types ◽  
Ventricular Outflow Tract ◽  
Left Ventricular ◽  
Differentially Expressed

Hypertrophic Cardiomyopathy (HCM) is a common inherited disorder characterized by unexplained left ventricular hypertrophy with or without left ventricular outflow tract (LVOT) obstruction. Single-nuclei RNA-sequencing (snRNA-seq) of both obstructive and nonobstructive HCM patient samples has revealed alterations in communication between various cell types, but no direct and integrated comparison between the two HCM phenotypes has been reported. We performed a bioinformatic analysis of HCM snRNA-seq datasets from obstructive and nonobstructive patient samples to identify differentially expressed genes and distinctive patterns of intercellular communication. Differential gene expression analysis revealed 37 differentially expressed genes, predominantly in cardiomyocytes but also in other cell types, relevant to aging, muscle contraction, cell motility, and the extracellular matrix. Intercellular communication was generally reduced in HCM, affecting the extracellular matrix, growth factor binding, integrin binding, PDGF binding, and SMAD binding, but with increases in adenylate cyclase binding, calcium channel inhibitor activity, and serine-threonine kinase activity in nonobstructive HCM. Increases in neuron to leukocyte and dendritic cell communication, in fibroblast to leukocyte and dendritic cell communication, and in endothelial cell communication to other cell types, largely through changes in the expression of integrin-β1 and its cognate ligands, were also noted. These findings indicate both common and distinct physiological mechanisms affecting the pathogenesis of obstructive and nonobstructive HCM and provide opportunities for the personalized management of different HCM phenotypes.

scholarly journals Common and Distinctive Intercellular Communication Patterns in Human Obstructive and Nonobstructive Hypertrophic Cardiomyopathy

2021 ◽  
Author(s):  
Christina J. Codden ◽  
Michael T. Chin
Keyword(s):  
Extracellular Matrix ◽  
Hypertrophic Cardiomyopathy ◽  
Dendritic Cell ◽  
Differentially Expressed Genes ◽  
Intercellular Communication ◽  
Cell Communication ◽  
Cell Types ◽  
Ventricular Outflow Tract ◽  
Left Ventricular ◽  
Differentially Expressed

Hypertrophic Cardiomyopathy (HCM) is a common inherited disorder characterized by unexplained left ventricular hypertrophy, with or without left ventricular outflow tract (LVOT) obstruction. Single nuclei RNA-sequencing (snRNA-seq) of both obstructive and nonobstructive HCM patient samples have revealed alterations in communication between various cell types but a direct and integrated comparison between the two HCM phenotypes has not been reported. We performed a bioinformatic analysis of HCM snRNA-seq datasets from obstructive and nonobstructive patient samples to identify differentially expressed genes and distinctive patterns of intercellular communication. Differential gene expression analysis revealed 37 differentially expressed genes, predominantly in cardiomyocytes but also in other cell types, relevant to aging, muscle contraction, cell motility and the extracellular matrix. Intercellular communication was generally reduced in HCM, affecting the extracellular matrix, growth factor binding, integrin binding, PDGF binding and SMAD binding, but with increases in adenylate cyclase binding, calcium channel inhibitor activity, and serine-threonine kinase activity in nonobstructive HCM. Increases in neuron to leukocyte and dendritic cell communication, in fibroblast to leukocyte and dendritic cell communication and in endothelial cell communication to other cell types, largely through changes in expression of integrin-b1 and its cognate ligands, were also noted. These findings indicate both common and distinct physiological mechanisms affecting the pathogenesis of obstructive and nonobstructive HCM and provide opportunities for personalized management of different HCM phenotypes.

scholarly journals Altered Intercellular Communication and Extracellular Matrix Signaling as a Potential Disease Mechanism in Human Hypertrophic Cardiomyopathy

2021 ◽  
Author(s):  
Amy Larson ◽  
Christina J Codden ◽  
Gordon S Huggins ◽  
Hassan Rastegar ◽  
Frederick Y Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Hypertrophic Cardiomyopathy ◽  
Intercellular Communication ◽  
Gene Expression Analysis ◽  
Left Ventricular Outflow Tract ◽  
Cell Types ◽  
Ventricular Outflow Tract ◽  
Left Ventricular ◽  
Left Ventricular Outflow

Objectives: To understand Hypertrophic Cardiomyopathy-associated alterations in gene expression and intercellular communication at the single cell level in left ventricular outflow tract lesions. Background: Human hypertrophic cardiomyopathy (HCM) is considered a disorder of the sarcomere (i.e., cardiomyocytes) but the paradoxical association of nonmyocyte phenotypes such as fibrosis, mitral valve anomalies and microvascular occlusion is unexplained. Methods: To understand the interplay between cardiomyocyte and nonmyocyte cell types in human HCM, single nuclei RNA-sequencing (snRNA-seq) was performed on myectomy specimens from HCM patients with left ventricular outflow tract obstruction and control samples from donor hearts free of cardiovascular disease. Results: Clustering analysis identified a total of 34 distinct cell populations, which were classified into 10 different cell types based on marker gene expression. Differential gene expression analysis comparing HCM to Normal datasets revealed differences in sarcomere and extracellular matrix gene expression. Analysis of expressed ligand-receptor pairs across multiple cell types indicated profound disruption in HCM intercellular communication, particularly between cardiomyocytes and fibroblasts, fibroblasts and lymphocytes and involving integrin β1 and its multiple extracellular matrix (ECM) cognate ligands. Conclusions: These findings provide evidence for intercellular interactions in HCM that link sarcomere dysfunction with altered cardiomyocyte secretion of ECM ligands, altered fibroblast ligand-receptor interactions with a variety of cell types and increased fibroblast to lymphocyte signaling, which can further alter the ECM composition, disrupt cellular function and promote nonmyocyte phenotypes.

scholarly journals Anesthetic Challenges in the Management of Intracranial Aneurysm Clipping in a Patient with Hypertrophic Cardiomyopathy

2020 ◽  
Author(s):  
Sakshi Duggal ◽  
Priyanka Khurana ◽  
Pragati Ganjoo ◽  
Nilima Das
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Perioperative Complications ◽  
Artery Aneurysm ◽  
Ventricular Outflow Tract ◽  
Left Ventricular ◽  
Anterior Communicating Artery ◽  
Drug Selection ◽  
Aneurysm Clipping ◽  
Left Ventricular Outflow ◽  
Life Threatening

AbstractAneurysmal surgeries are high-risk procedures due to potential for occurrence of fatal perioperative complications. This risk is exaggerated in the presence of co-existing hypertrophic cardiomyopathy (HCM). It involves asymmetrical hypertrophy of left ventricle with mitral valve dysfunction, leading to left ventricular outflow tract obstruction. Various perioperative factors may precipitate this obstruction resulting in life-threatening consequences. We report the management of a patient with HCM undergoing anterior communicating artery aneurysm clipping and discuss the anesthetic concerns. Comprehensive approach with careful drug selection, vigilant monitoring, and preparedness for complications enabled patient safety and a good neurological outcome.

Angina Pectoris Due to Severe Muscular Bridge in Hypertrophic Cardiomyopathy

1998 ◽  
Vol 6 (2) ◽  
pp. 132-134
Author(s):  
M Şah Topcuoĝlu ◽  
Ayhan Usal ◽  
Cem Kayhan ◽  
Aladdin Pekedis ◽  
Acar Tokcan ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Calcium Antagonist ◽  
Hypertrophic Cardiomyopathy ◽  
Angina Pectoris ◽  
Left Ventricular Outflow Tract ◽  
Young Patients ◽  
Ventricular Outflow Tract ◽  
Myocardial Scintigraphy ◽  
Left Ventricular ◽  
Left Ventricular Outflow

We report the case of a 39-year-old male with hypertrophic cardiomyopathy who complained of angina pectoris. The patient was treated with a beta blocker and a calcium antagonist without effect. Myocardial scintigraphy revealed anterior ischemia. Cardiac catheterization and ventriculography revealed severe systolic narrowing of the left anterior descending coronary artery and no significant pressure gradient across the left ventricular outflow tract. Myotomy was performed on a muscular bridge over the left anterior descending coronary artery and the patient's angina was relieved. In young patients with hypertrophic cardiomyopathy who develop angina refractory to medical therapy, a coexisting muscular bridge should be sought.

Identification of Differentially Expressed Genes in Human Varicose Veins: Involvement of Matrix Gla Protein in Extracellular Matrix Remodeling

2007 ◽  
Vol 44 (6) ◽  
pp. 444-459 ◽  
Author(s):  
Chrystelle Cario-Toumaniantz ◽  
Cédric Boularan ◽  
Leon J. Schurgers ◽  
Marie-Françoise Heymann ◽  
Martine Le Cunff ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Differentially Expressed Genes ◽  
Varicose Veins ◽  
Matrix Gla Protein ◽  
Differentially Expressed ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling

Long-Living Budding Yeast Cell Subpopulation Induced by Ethanol/Acetate and Respiration

2019 ◽  
Vol 75 (8) ◽  
pp. 1448-1456 ◽  
Author(s):  
Young-Yon Kwon ◽  
Seung-Soo Kim ◽  
Han-Jun Lee ◽  
Seo-Hyeong Sheen ◽  
Kyoung Heon Kim ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Budding Yeast ◽  
Gradient Centrifugation ◽  
Carbon Sources ◽  
Cell Types ◽  
Glucose Sensing ◽  
Differentially Expressed ◽  
Cell Subpopulation ◽  
Genes Encoding ◽  
Cell Transcriptome

Abstract Budding yeast generate heterogeneous cells that can be separated into two distinctive cell types: short-living low-density and long-living high-density (HD) cells by density gradient centrifugation. We found that ethanol and acetate induce formation of HD cells, and mitochondrial respiration is required. From their transcriptomes and metabolomes, we found upregulated differentially expressed genes in HD cells involved in the RGT2/RGT1 glucose sensing pathway and its downstream genes encoding hexose transporters. For HD cells, we determined an abundance of various carbon sources including glucose, lactate, pyruvate, trehalose, mannitol, mannose, and galactose. Other upregulated differentially expressed genes in HD cells were involved in the TORC1–SCH9 signaling pathway and its downstream genes involved in cytoplasmic translation. We also measured an abundance of free amino acids in HD cells including valine, proline, isoleucine, and glutamine. These characteristics of the HD cell transcriptome and metabolome may be important conditions for maintaining a long-living phenotype.

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