"Immunoregulation in Atherosclerosis: A Single-Cell RNA Sequencing Study"

June 9, 2025 updated by: Carlos Vicente Serrano Junior, Hospital Israelita Albert Einstein

The Architectural Immunoregulation in Atherosclerotic Disease: A Single-Cell RNA Sequencing and Spatial Biology Approach

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Observational

Enrollment (Estimated)

30

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Brazil
    • SP
      • São Paulo, SP, Brazil, 05652-900
        • Hospital Israelita Albert Einstein

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Patients diagnosed with ischemic cardiomyopathy due to advanced atherosclerosis, undergoing heart transplantation.

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Coronary Plaques from Explanted Heart
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.
Diagnostic test: Single Cell RNA Sequencing

Reprocessing

Data normalization, dimensionality reduction, and clustering will be performed using the Seurat package (based on R).

Cell types will be identified based on canonical marker gene expression. Cell Subpopulation Identification

Clusters will be annotated based on signatures of known cell types (e.g., endothelial cells, smooth muscle cells, macrophages, etc.).

Differential gene expression analysis will be conducted to identify disease-associated genes.

Pathway and Function Enrichment

Gene Set Enrichment Analysis (GSEA) and pathway analyses (e.g., KEGG, Reactome) will be carried out to investigate the biological processes and pathways driving atherosclerosis.

Quality Control

Sequencing reads will be assessed for quality using FASTQC, and low-quality reads will be filtered out.

The Cell Ranger software (10x Genomics) will be used to align reads to the human genome and quantify gene expression at the single-cell level.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Concentration of Specific Cells Clusters And Macrophage / Linfocite Subpopulations : Create a high-resolution single-cell atlas of atherosclerotic plaques.
Time Frame: 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.
Through study completion, an average of 1 year and a half.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Concentration of interleukins and cellular subtypes by citometer flow to Identification of molecular signatures in atherosclerosis
Time Frame: Through study completion, an average of 1 year and a half .
The secondary objective is to identify molecular signatures that reveal individual predispositions to specific phenotypes, such as susceptibility to atherosclerosis, response to therapies, and other health characteristics, establishing the foundation for precision medicine and population health studies in Brazil by determining specific concentrations of pro and anti-inflammatory molecules and cell types.
Through study completion, an average of 1 year and a half .

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Israelita Albert Einstein

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 25, 2025

Primary Completion (Estimated)

October 25, 2026

Study Completion (Estimated)

April 25, 2027

Study Registration Dates

First Submitted

February 24, 2025

First Submitted That Met QC Criteria

February 28, 2025

First Posted (Actual)

March 6, 2025

Study Record Updates

Last Update Posted (Actual)

June 10, 2025

Last Update Submitted That Met QC Criteria

June 9, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AteroImunoHIAE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The scRNA-seq data and R scripts used in the analysis of this study will be available from the corresponding author upon request.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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