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Cardiomyopathy III: Hypertrophic Cardiomyopathy01:29

Cardiomyopathy III: Hypertrophic Cardiomyopathy

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Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
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Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

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Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
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Cardiomyopathy I: Introduction and Classification01:25

Cardiomyopathy I: Introduction and Classification

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Cardiomyopathy, or CMP, is a group of diseases affecting the myocardial structure, impairing its ability to pump blood effectively. This condition can lead to arrhythmias, heart failure, or sudden cardiac death.Cardiomyopathies are classified into primary and secondary categories:Primary Cardiomyopathy refers to conditions involving only the heart muscle that are often idiopathic (of unknown cause) or genetic. They primarily affect the myocardium without the involvement of other systemic...
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Heart Failure II: Pathophysiology01:29

Heart Failure II: Pathophysiology

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Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...
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Feedback Regulation of Calcium Concentration

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Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
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Pathophysiology of Heart Failure01:17

Pathophysiology of Heart Failure

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Heart failure (HF) is a progressive syndrome involving ventricles that leads to inadequate cardiac output. It can be classified based on location and output or ejection fraction. Ejection fraction (EF) is an essential measurement in the diagnosis and surveillance of HF. Reduced EF corresponds to systolic heart failure (HFrEF). However, HF with preserved ejection fraction (HFpEF) is becoming increasingly prevalent. Also known as diastolic HF, this form of HF is related to aging. The...
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  1. ホーム
  2. 研究分野
  3. 生物医学と臨床科学
  4. 心血管医学と血液学
  5. 心臓病 (心血管疾患を含む)
  6. ヒト高縮性心筋病における遺伝子型依存性および独立性カルシウムシグナリング不調
  1. ホーム
  2. 研究分野
  3. 生物医学と臨床科学
  4. 心血管医学と血液学
  5. 心臓病 (心血管疾患を含む)
  6. ヒト高縮性心筋病における遺伝子型依存性および独立性カルシウムシグナリング不調

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Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
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Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model

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ヒト高縮性心筋病における遺伝子型依存性および独立性カルシウムシグナリング不調

Adam S Helms1, Francisco J Alvarado2, Jaime Yob2

  • 1From Departments of Internal Medicine (A.S.H., J.Y., V.T.T., H.H.V., S.M.D.), Molecular and Integrative Physiology (F.J.A., H.H.V., S.M.D.), Cardiac Surgery (F.P.), and Pediatrics (M.W.R.), University of Michigan, Ann Arbor. adamhelm@med.umich.edu.

Circulation
|October 1, 2016

PubMed で要約を見る

まとめ
この要約は機械生成です。

異常なカルシウムシグナル伝達には,異なる経路が含まれる. サルコメア変異陽性HCMはCaMKII経路の活性化を示し,すべてのHCMはSERCA2A機能を低下させる.

キーワード:
カルシウムカルシウムカルモジュリン依存タンパク質キナーゼ2型心筋病 縮症

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科学分野:

  • 心血管生物学
  • 分子心臓科
  • 生物化学

背景:

  • 異常なカルシウムシグナル伝達は,高縮性心筋病 (HCM) の病原性に関与している.
  • サルコメア遺伝子の変異は,心臓のカルシウム処理経路を独特に破壊する可能性があります.

研究 の 目的:

  • 人間のHCMにおけるカルシウム調節経路の変化を調査する.
  • サルコメアの変異状態に基づいて経路の変化を区分する.

主な方法:

  • ヒトHCMサンプル (n=35) と対照群 (n=8) の遺伝子発現,タンパク質レベル,機能検査の分析.
  • SERCA2A,フォスフォランバン,CaMKIIを含む主要なカルシウム処理タンパク質に焦点を当てます.
  • カルシヌーリンとライオノジン受容体の経路の評価

主要な成果:

  • CaMKII (カルシウム/カルモジュリン依存タンパク質キナーゼII型) 経路の活性化,特にpT17- fosfolambanの増加は,サルコメア変異のHCMにおいてのみ発生した.
  • ゲノタイプに関係なく,すべてのHCM症例において,SERCA2A (サルコプラズマ内網状カルシウムATPase2) の発現と機能が低下した.
  • カルシヌーリンや心臓のライオノジン受容体の有意な変化は認められなかった.
遺伝学
サルコメア
サルコプラズマの網膜にカルシウムを運ぶATPases

結論:

  • HCMは,一般的なメカニズムと遺伝子型特有のメカニズムの両方を介してカルシウムを誤って処理することを示す.
  • 翻訳後のCaMKII活性化は,サルコメア変異陽性HCMの特徴です.
  • SERCA2A機能の低下とサルコプラズマ網膜のカルシウム吸収は,全体的にHCMの特徴です.