增加血管衰老和受损的内皮原生细胞功能,由昼夜基因Per2突变介导
Chao-Yung Wang1, Ming-Shien Wen, Hong-Wei Wang
1Brigham and Women's Hospital, 65 Landsdowne St, Room 275, Cambridge, MA 02139, USA.
Circulation
|November 5, 2008
概括
循环基因Per2突变通过促进细胞衰老和减少内皮前代细胞功能,损害了血管修复. 恢复Per2功能可以改善缺血后的复血管.
科学领域:
- 心血管生物学 心血管生物学
- 循环节律是指循环节律的节奏.
- 血管生物学 血管生物学
背景情况:
- 循环节律障碍和血管衰老与心血管疾病有关.
- 昼夜基因Per2调节内皮依赖血管运动,但其在内皮功能中的机制尚不清楚.
- Per2突变可能会通过血管衰老和受损的内皮原生细胞 (EPC) 功能引起内皮功能障碍.
研究的目的:
- 研究昼夜基因Per2在内皮功能和血管修复中的作用.
- 为了确定是否Per2缺乏导致血管衰老和损害EPC功能.
- 阐明Per2突变影响重血管化的机制.
主要方法:
- 在Per2突变 (Per2(m/m)) 和野生型小鼠中比较了内皮细胞和血管功能.
- 评估了血管衰老,Akt信号传递和内皮细胞中的网络形成.
- 利用后肢缺血模型和骨髓移植来研究EPC动员和功能.
- 通过matrigel植入和恢复血液流量的评估新血管化.
主要成果:
- 每2 (m/m) 内皮细胞显示Akt信号增加,衰老,并减少增殖和网络形成.
- 每2m/m的小鼠表现出血流恢复受损,新血管化和缺血后四肢自动截肢.
- 在对缺血症或VEGF.的反应中,EPC动员在Per2(m/m) 小鼠中受损.
- 野生类型的EPC移植恢复了血液流动,并防止了Per2{m/m}小鼠的自动截肢.
结论:
- Per2突变诱导了Akt-依赖的血管衰老.
- 由于Per2突变而导致的EPC功能受损,阻碍了缺血引起的再血管化.
- 准Per2可能为血管修复和心血管疾病提供治疗策略.
相关概念视频
02:19Circadian Rhythms and Gene Regulation
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
02:19Circadian Rhythms and Gene Regulation
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
01:15Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response
Circadian rhythms are cyclic changes that are crucial in plasma drug concentrations. Various standard circadian parameters, including core body temperature, heart rate, and other cardiovascular factors, directly impact disease states and the therapeutic response to drug therapy.
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...
01:24Regulation of Angiogenesis and Blood Supply
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 hydroxylase and factor...
02:15Replicative Cell Senescence
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
02:15Replicative Cell Senescence
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...