卵管内グリコタンパク質1は,MYH9との相互作用によって血管再構成を誘導することによって高血圧を促進する
Congxia Bai1,2, Ming Su3, Yaohua Zhang1,4
1State Key Laboratory of Cardiovascular Disease, Fuwai Hospital (C.B., Y.Z., Y.S., L.S., N.X., H.X., H.W., M.Z., J.P., J.L., R.H., H.L., J.C.), National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Circulation
|September 29, 2022
まとめ
卵巣糖タンパク質1 (OVGP1) はDNA低甲基化によって高血圧に関連しています. OVGP1はMYH9と相互作用することで,血管の改造と機能障害を促進し,高血圧対策因子として識別します.
科学分野:
- 心血管生物学
- エピジェネティクス
- 分子医学
背景:
- 高血圧は,遺伝的および環境的要因によって影響される,不明なメカニズムを持つ一般的な心血管疾患です.
- DNAメチル化というエピジェネティックな改変は 環境の影響と遺伝子発現を結びつけ 高血圧を理解するのに不可欠です
- 高血圧患者の差異性DNAメチル化に対するスクリーニングは,疾患メカニズムの解明に不可欠です.
研究 の 目的:
- 高血圧におけるDNAメチル化の役割を調査する.
- 高血圧の発達に関与する特定の遺伝子と分子経路を特定する.
- 血圧の調節と血管再構築におけるOVGP1の機能的重要性を調査する.
主な方法:
- Illumina 450K BeadChipとパイロシーケンシングを用いた全ゲノムDNAメチル化スクリーニング
- 血OVGP1濃度に対する酵素関連免疫吸収検査 (ELISA)
- 血圧測定と血管研究を含む,Ovgp1トランスジェニックとノックアウトマウスの生成と分析.
- OVGP1の相互作用相手を特定するために,タンパク質とタンパク質の相互作用測定法 (プルダウン,質量スペクトロメトリ,共免疫プレシピテーション)
主要な成果:
- OVGP1プロモーターの低メチル化部位 (cg20823859) は高血圧患者のOVGP1濃度の上昇と関連していた.
- マウスのOVGP1過剰発現は高血圧,血管機能障害,再構成,酸化ストレス,炎症を引き起こした.
- OVGP1欠乏症はアンジオテンシンIIによる血管損傷を緩和した.
- OVGP1はMYH9と相互作用し,MYH9の抑制はOVGP1誘発の高血圧と血管再構成を減少させた.
結論:
- OVGP1プロモーターの低メチル化により,OVGP1が上昇し,高血圧に寄与する.
- OVGP1はMYH9との相互作用によって血管再構成と機能不全を促進することによって,高血圧抑制因子として作用する.
- OVGP1- MYH9の相互作用をターゲットにすることが,高血圧の治療戦略を提供することができる.
関連する概念動画
Hypertension II: Pathophysiology
56
Hypertension is a chronic condition in which the blood's force against artery walls is excessively high, posing risks such as heart disease. The condition's underlying mechanisms involve complex interactions among the cardiovascular, kidney, and autonomic nervous systems.Renin-Angiotensin-Aldosterone System (RAAS): This system significantly influences blood pressure regulation. When blood pressure decreases, the kidneys secrete renin. This enzyme transforms angiotensinogen, a plasma protein,...
56
Hormonal Regulation of Blood Pressure
3.1K
Endocrinal or hormonal intervention in the cardiovascular system is predominantly exerted by the catecholamines - epinephrine and norepinephrine, as well as a slew of hormones that interact with renal function to modulate blood volume.
Epinephrine and Norepinephrine
The adrenal medulla releases epinephrine and norepinephrine, catecholamines that enhance and extend the sympathetic or "fight or flight" physiological response. These hormones escalate heart rate and the force of contraction...
Epinephrine and Norepinephrine
The adrenal medulla releases epinephrine and norepinephrine, catecholamines that enhance and extend the sympathetic or "fight or flight" physiological response. These hormones escalate heart rate and the force of contraction...
3.1K
Hypertension and Regulation of Blood Pressure
2.3K
Hypertension, the most common cardiovascular disease, is diagnosed through repeated measurements of elevated blood pressure. Its risks, including damage to the kidney, heart, and brain, are directly proportional to blood pressure levels. Starting from 115/75 mm Hg, the risk of cardiovascular disease doubles with each increment of 20/10 mm Hg. The diagnosis relies on blood pressure measurements, not on patient symptoms, as hypertension is often asymptomatic until end-organ damage is imminent or...
2.3K
Regulation of Angiogenesis and Blood Supply
2.7K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.7K
Hypertension I: Introduction
56
Hypertension is a widespread, long-term medical condition where blood pressure in the arteries remains elevated. It is characterized by systolic blood pressure readings of 130 mm Hg or above or diastolic blood pressure (DBP) readings of 80 mm Hg or higher. Unmanaged hypertension poses significant health risks, making the distinction between primary (or essential) hypertension and secondary hypertension crucial, as their management and implications vary.Primary HypertensionPrimary hypertension,...
56
Hormonal Regulation
33.6K
The renin-aldosterone system is an endocrine system which guides the renal absorption of water and electrolytes, thus managing blood pressure and osmoregulation. Activation of the system begins in the kidneys with a small cluster of cells adjacent to the afferent and efferent blood vessels of the renal corpuscle. As the nephrons are filtering blood, juxtaglomerular cells monitor blood pressure. If they detect a decrease in pressure, they release the hormone renin into the bloodstream.
33.6K


