表观遗传机制在雄性和雌性Npr1杂型小鼠中差异调节血压和功能障碍
Prerna Kumar1, Kandasamy Neelamegam1, Chandramohan Ramasamy1
1Department of Physiology, School of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana, USA.
概括
血压和功能的表观遗传调节在两性之间存在差异. 基斯脱乙酶抑制剂治疗改善了小鼠的高血压和功能障碍,观察到性别特异性的效应.
科学领域:
- 心血管科学 心血管科学
- 腎臟病學 (nephrology) 是一種醫學專業.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 关利基环酶/尿性受体-A (GC-A/NPRA) 信号传递对于调节血压和功能至关重要.
- 表观遗传机制,包括基因组修饰,越来越多地被认为在心血管和脏疾病中的作用.
- 高血压和病的发病率和严重程度的性别特异性差异表明存在潜在的生物学变异.
研究的目的:
- 研究基因向小鼠中调节平均动脉压 (MAP) 和功能障碍的表观遗传机制.
- 为了确定一类1组胺脱乙酶抑制剂 (HDACi) 的性别特异性影响,莫塞丁诺斯塔特 (MGCD),在表观遗传变化,血压和功能.
主要方法:
- 成年雄性和雌性小鼠具有不同的Npr1基因拷贝数 (1,2,或3个拷贝) 被用MGCD治疗了14天.
- 测量包括血压 (BP),功能 (肌素清除率),组织病理学和表观遗传标记 (基因素乙化/甲基化,基因/蛋白质表达).
- 还评估了NF-κB局部化和DNA结合活性.
主要成果:
- 与对照组相比,一副本的雄性小鼠表现出明显更高的MAP,功能障碍和纤维化.
- 在单拷贝小鼠中,HDAC1/2,原1α-2 (Col1α-2) 和α光滑肌动蛋白 (α-SMA) 的水平升高.
- MGCD治疗降低了血压,改善了功能,并修复了组织病理,在男性和女性之间观察到纤维化,蛋白尿和NF-κB抑制方面的差异效应.
结论:
- 表观遗传机制在调节MAP和功能障碍方面发挥着重要作用.
- 用MGCD抑制1类HDAC表明了对高血压和功能障碍的治疗潜力.
- 针对表观遗传途径为心血管和脏疾病的性别特异性治疗提供了一个有希望的策略.
相关概念视频
01:18Hypertension and Regulation of Blood Pressure
2.0K
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...
2.0K
01:17Hormonal Regulation of Blood Pressure
2.5K
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...
2.5K
01:33Hormonal Regulation
33.0K
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.
33.0K
01:28Factors affecting Blood pressure
3.1K
Several physiological and lifestyle factors influence blood pressure (BP). Understanding these factors is crucial as they are significant in patient education and blood pressure management.
Physiological Factors:
Physiological Factors:
3.1K
01:18Neural Regulation of Blood Pressure
2.7K
The neural regulation of blood pressure involves intricate interactions between the autonomic nervous system (ANS) and cardiovascular system, ensuring adequate perfusion of tissues. This regulation primarily occurs through baroreceptor and chemoreceptor reflexes, involving both short-term and long-term mechanisms.
Baroreceptor Reflex
Baroreceptors, located in the carotid sinuses and aortic arch, detect changes in blood pressure. When blood pressure rises, these stretch-sensitive receptors...
Baroreceptor Reflex
Baroreceptors, located in the carotid sinuses and aortic arch, detect changes in blood pressure. When blood pressure rises, these stretch-sensitive receptors...
2.7K
01:28Glomerular Filtration Rate and its Regulation
2.4K
The Glomerular Filtration Rate (GFR) is a measure of kidney function, reflecting the volume of filtrate formed per minute in the kidneys. On average, GFR is approximately 125 mL/min in males and 105 mL/min in females. Maintaining a relatively constant GFR is essential for the kidneys to effectively regulate body fluid homeostasis and maintain extracellular stability.
GFR regulation involves two primary intrinsic controls: the myogenic and tubuloglomerular feedback mechanisms.
The myogenic...
GFR regulation involves two primary intrinsic controls: the myogenic and tubuloglomerular feedback mechanisms.
The myogenic...
2.4K