AI Article Synopsis
- The study investigates the role of estrogen in regulating Lipoprotein(a) (Lp(a)), which is linked to cardiovascular disease, particularly focusing on how it affects vascular remodeling in high Lp(a) concentration.
- Research was conducted using Lp(a) transgenic mice, showing that estrogen deficiency from ovariectomy increased Lp(a) levels and vascular issues, while estrogen replacement helped reverse these effects.
- The findings suggest that estrogen may not only lower plasma Lp(a) levels but also mitigate vascular remodeling induced by Lp(a), highlighting its potential as a therapeutic option.
Article Abstract
Objective: Although it is well known that Lipoprotein(a) (Lp(a)) is an atherogenic lipoprotein and an independent risk factor for cardiovascular disease, there is no confirmed therapy to decrease Lp(a) or prevent atherosclerosis induced by Lp(a). Thus, it is mandatory to develop novel therapy to prevent atherosclerosis in high Lp(a) concentration. Here, we focused on the effect of estrogen on Lp(a) level and Lp(a)-induced vascular remodeling.
Methods: We employed Lp(a) transgenic mice (human apo(a) yeast artificial chromosome (YAC) and human apoB double transgenic mice). Vascular remodeling was induced by ligation of the common carotid artery and the effect of estrogen was evaluated in female mice after ovariectomy with or without estrogen replacement.
Results: Estrogen deficiency caused by ovariectomy increased serum Lp(a), and continuous replacement of 17beta-estradiol (20 microg/kg/day) reversed the change. In the vascular remodeling model induced by carotid artery occlusion, neointima formation was significantly increased in ovariectomized female Lp(a) transgenic mice, but few in male Lp(a) transgenic mice, as compared to wild FVB mice. Importantly, continuous replacement of estrogen in ovariectomized mice significantly attenuated it. In cultured endothelial cells and macrophages, addition of Lp(a) increased mRNA of ICAM-1, VCAM-1, E-selectin and MCP-1 in endothelial cells and TNF-alpha, IL-1beta and MCP-1 in macrophages in a dose-dependent manner. Importantly, pre-treatment with estrogen attenuated these changes in a dose-dependent manner.
Conclusion: Estrogen negatively regulates both plasma Lp(a) level and Lp(a)-induced vascular remodeling, suggesting that estrogen might be a strong candidate to reduce serum Lp(a) concentration.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.atherosclerosis.2010.01.016 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Photoacoustic and fluorescence dual-modality imaging of cerebral biomarkers in Alzheimer's disease rodent model.
J Biomed Opt
December 2024
University of Michigan, Department of Biomedical Engineering, Ann Arbor, Michigan, United States.
Significance: Alzheimer's disease (AD) is a predominant form of dementia that can lead to a decline in the quality of life and mortality. The understanding of the pathological changes requires monitoring of multiple cerebral biomarkers simultaneously with high resolution. Photoacoustic microscopy resolves single capillaries, allowing investigations into the most affected types of vessels.
View Article and Find Full Text PDFVascular Smooth Muscle Cells Transdifferentiate into Chondrocyte-Like Cells and Facilitate Meniscal Fibrocartilage Regeneration.
Research (Wash D C)
December 2024
Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing, China.
The effective and translational strategy to regenerate knee meniscal fibrocartilage remained challenging. Herein, we first identified vascular smooth muscle cells (VSMCs) transdifferentiated into fibrochondrocytes and participated in spontaneous meniscal regeneration using smooth muscle cell lineage tracing transgenic mice meniscal defect model. Then, we identified low-intensity pulsed ultrasound (LIPUS) acoustic stimulus enhanced fibrochondrogenic transdifferentiation of VSMCs in vitro and in vivo.
View Article and Find Full Text PDFIdentification of Pappa and Sall3 as Gli3 direct target genes acting downstream of cilia signaling in corticogenesis.
Cereb Cortex
December 2024
Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
The cerebral cortex is critical for advanced cognitive functions and relies on a vast network of neurons to carry out its highly intricate neural tasks. Generating cortical neurons in accurate numbers hinges on cell signaling orchestrated by primary cilia to coordinate the proliferation and differentiation of cortical stem cells. While recent research has shed light on multiple ciliary roles in corticogenesis, specific mechanisms downstream of cilia signaling remain largely unexplored.
View Article and Find Full Text PDFMicroglial cell proliferation is regulated, in part, by reactive astrocyte ETB signaling after ischemic stroke.
Exp Neurol
December 2024
Department of Medicine, Cardiovascular Research Institute, University of Vermont, Colchester, VT 05446, USA; Department of Neurological Sciences and Neuroscience Graduate Program, University of Vermont, Burlington, VT 05401, USA. Electronic address:
Reciprocal communication between reactive astrocytes and microglial cells provides local, coordinated control over critical processes such as neuroinflammation, neuroprotection, and scar formation after CNS injury, but is poorly understood. The vasoactive peptide hormone endothelin (ET) is released and/or secreted by endothelial cells, microglial cells and astrocytes early after ischemic stroke and other forms of brain injury. To better understand glial cell communication after stroke, we sought to identify paracrine effectors produced and secreted downstream of astroglial endothelin receptor B (ETB) signaling.
View Article and Find Full Text PDFAccumulated BCAAs and BCKAs contribute to the HFD-induced deterioration of Alzheimer's disease via a dysfunctional TREM2-related reduction in microglial β-amyloid clearance.
J Neuroinflammation
December 2024
Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People's Republic of China.
A high-fat diet (HFD) induces obesity and insulin resistance, which may exacerbate amyloid-β peptide (Aβ) pathology during Alzheimer's disease (AD) progression. Branched-chain amino acids (BCAAs) accumulate in obese or insulin-resistant patients and animal models. However, roles of accumulated BCAAs and their metabolites, branched-chain keto acids (BCKAs), in the HFD-induced deterioration of AD and the underlying mechanisms remains largely unclear.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!