The Architectural Immunoregulation in Atherosclerotic Disease: A Single-Cell RNA Sequencing and Spatial Biology Approach
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Concentration of Specific Cells Clusters And Macrophage / Linfocite Subpopulations : Create a high-resolution single-cell atlas of atherosclerotic plaques.
研究概览
简要总结
Atherosclerosis is the leading cause of acute cardiovascular events, such as myocardial infarction and stroke, and is a significant risk factor for cardiovascular mortality. The detailed understanding of the immune mechanisms and cellular transformations involved in the pathogenesis of atherosclerosis is still limited, and the use of single-cell RNA sequencing (scRNAseq) has revealed new cellular functions and subpopulations associated with disease progression. This study aims to identify cellular subpopulations, molecular pathways, and changes in gene expression related to the development of atherosclerosis in human coronary arteries. Using scRNAseq, the study seeks to characterize the transcriptomic landscape of cells present in atherosclerotic plaques and identify molecular signatures that reveal individual predispositions to specific phenotypes, such as disease susceptibility and response to therapies. The research will be conducted at the Albert Einstein Israeli Hospital in São Paulo and will involve samples from coronary arteries and atherosclerotic plaques of the explanted hearts of patients who have undergone heart transplants as well as from discarded material of coronary artery bypass graft surgery (CABG). With an estimated sample size of 20-30 plaques, the data obtained will allow for a detailed analysis of the molecular mechanisms involved in atherosclerosis, contributing to the development of specific therapeutic targets.
详细描述
This is a prospective observational study that will be conducted with samples of coronary arteries and atherosclerotic plaques from the explanted hearts of patients with ischemic cardiomyopathy who have undergone heart transplants as well as from discarded material of coronary artery bypass graft surgery . The atherosclerotic plaque samples will be retrieved from the coronary arteries during the transplant surgery or the CABG procedure and transported to the laboratory within 2 hours. The selected arteries will be dissected and microscopically evaluated, and the samples will be fixed in formalin, embedded in paraffin, and stained for histological analysis. The tissue will be enzymatically dissociated to obtain individual cells, which will then be filtered and assessed for cell viability. The cells will undergo single-cell RNA sequencing (scRNAseq) with the aim of analyzing around 5,000-10,000 cells per sample. The sample size will be 20-30 plaques, with the goal of capturing the main cellular populations and performing a robust analysis.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 45 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients diagnosed with ischemic cardiomyopathy due to advanced atherosclerosis, undergoing heart transplantation;
- •Patients with coronary artery disease submitted to coronary artery bypass graft surgery (CABG)."
- •Aged between 40 and 75 years;
- •Signed informed consent form.
排除标准
- •Patients with systemic inflammatory or autoimmune diseases;
- •History of cancer within the last 5 years or active malignancy;
- •Recent use (within the last 6 months) of immunosuppressive therapy.
结局指标
主要结局
Concentration of Specific Cells Clusters And Macrophage / Linfocite Subpopulations : Create a high-resolution single-cell atlas of atherosclerotic plaques.
时间窗: Through study completion, an average of 1 year and a half.
Determine the concentration of cellular clusters with specific inflammatory subpopulations determination to Create a high-resolution single-cell atlas of atherosclerotic plaques, revealing cell-specific transcriptional changes associated with the disease. The findings could identify new therapeutic targets for intervention in atherosclerosis and enhance the understanding of its molecular pathogenesis.
次要结局
- Concentration of interleukins and cellular subtypes by citometer flow to Identification of molecular signatures in atherosclerosis(Through study completion, an average of 1 year and a half .)
研究者
Carlos Vicente Serrano Junior
Principal Investigator
Hospital Israelita Albert Einstein