胰岛素样生长因子结合蛋白-7 (IGFBP7) 将衰老与心力衰竭联系在一起
Liyong Zhang1, David Smyth1, Mohammad Al-Khalaf1
1University of Ottawa Heart Institute, Ottawa, ON, Canada.
Nature cardiovascular research
|August 28, 2024
概括
胰岛素样生长因子结合蛋白7 (IGFBP7) 通过促进心脏衰老和炎症,加剧心力衰竭 (HF). 向IGFBP7为HF患者与年龄相关的心脏衰退提供了潜在的治疗策略.
科学领域:
- 心血管研究研究心血管研究
- 分子生物学分子生物学
- 衰老研究研究 衰老研究
背景情况:
- 心力衰竭 (HF) 代表着日益严重的全球心血管健康危机,特别影响着老龄化人口.
- 与年龄有关的心脏功能障碍需要新的,精确的治疗干预措施.
- 慢性炎症是HF进展的关键驱动因素.
研究的目的:
- 调查胰岛素样生长因子结合蛋白7 (IGFBP7) 在心力衰竭的病变发生过程中的作用.
- 探索IGFBP7作为与年龄相关的心脏衰退的潜在治疗点.
主要方法:
- 在人类HF患者和压力过载小鼠模型中分析IGFBP7表达.
- 研究Igfbp7缺乏和降低对小鼠心脏功能,炎症,纤维化和衰老的影响.
- 使用AAV9-shRNA进行向心脏肌细胞Igfbp7的淘汰.
- 在体内使用抗体介导的IGFBP7中和.
主要成果:
- 心脏和血液IGFBP7水平在HF患者和模型中显著升高.
- 在小鼠HF模型中,Igfbp7缺乏减轻了心脏功能障碍,炎症,纤维化和衰老.
- 发现IGFBP7通过抑制FOXO3a促进心脏衰老,损害DNA修复和ROS排毒.
- 心肌IGFBP7直接影响病态心脏重塑,其中和逆转了小鼠的HF进展.
结论:
- 通过促进心脏衰老和炎症,IGFBP7在加速心力衰竭进展方面发挥着直接作用.
- 准IGFBP7及其相关的衰老途径为心力衰竭提供了一个有希望的治疗途径.
相关概念视频
01:17Pathophysiology of Heart Failure
1.5K
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...
1.5K
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
404
The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
404
01:22PI3K/mTOR/AKT Signaling Pathway
3.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.4K
01:28Insulin: The Receptor and Signaling Pathways
1.2K
Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
1.2K
01:26Aging
40
Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in aging.
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
40