Role of Endothelial Progenitor Cells Dysregulation and Inflammation in the Pathophysiology of Cardiovascular Complications of Type 2 Diabetes

This study aims to isolate endothelial progenitor cells (EPCs) from participants with type 2 diabetes (T2D) and cardiovascular complications and to comprehensively characterize EPC dysfunction. Specifically, the study will evaluate maladaptive angiocrine signaling, calcium signaling pathways, and the role of inflammation in EPC function and the progression of atherosclerosis during T2D development. A sub-study will assess EPC functionality by examining endothelial nitric oxide synthase (eNOS) expression and activity, as well as the effectiveness of in vitro eNOS gene enhancement.

Study Overview

• Status: Recruiting
• Conditions: Diabete Type 2; Cardio Vascular Disease

Detailed Description

Type 2 diabetes (T2D) is associated with damage to blood vessels, which can lead to serious complications such as heart disease, stroke, and other vascular problems.

Endothelial progenitor cells (EPCs) help maintain healthy blood vessels by repairing vascular injury. In people with T2D, the number and function of these cells are reduced, which may contribute to poor blood vessel repair and increased cardiovascular risk. The mechanisms responsible for this dysfunction are not fully understood. This study aims to examine how changes in cell signaling and chronic low-grade inflammation in T2D affect EPC function. EPCs will be isolated from patients with T2D, with and without cardiovascular complications, to assess their signaling properties, function, and ability to mature into vascular cells.

An in vitro sub-study will evaluate a potential therapeutic strategy to improve EPC function by increasing the activity of endothelial nitric oxide synthase (eNOS), a protein that plays a key role in maintaining healthy blood vessels. Reduced eNOS activity is an important contributor to vascular dysfunction in diabetes. Enhancing eNOS expression and function in EPCs may improve their regenerative capacity and help prevent or treat diabetic vascular complications.

• Study Type: Observational
• Enrollment (Estimated): 90

Contacts and Locations

Study Locations

• Qatar
  • Doha, Qatar
    • Recruiting
    • Hamad Medical Corporation
    • Contact: Jassim Al Suwaidi, MD; Phone Number: +974 4439 5354; Email: jalsuwaidi@hamad.qa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from Hamad Medical Corporation.

Description

Inclusion Criteria:

• T2D
• Males and females
• Older than 18 years of age
• Willingness to participate in the study and provide written consent form
• Consent to having peripheral blood withdrawals and urine collection for the study requirement.

Exclusion Criteria:

• Unable to meet the inclusion criteria
• Type I diabetes, MODY diabetes or other form of diabetes
• Active infection, inflammation, cancer or acute illness of any kind (other than a cardiovascular complication of diabetes if applicable in the group they are assigned to).
• Chronic inflammation (eg. auto-immune diseases) or infections (eg. HIV, chronic hepatitis).
• Evidence of malignancy within the past 5 years

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Groupe 1: T2D and no established cardiovascular complications; HbA1C level ≥ 6.5% and a fasting glucose level ≥126 mg/dl (7.0 mmol/l); No concomitant cardiovascular complications (coronary artery disease, stroke, nephropathy, retinopathy, peripheral arterial disease) per the history, medical records and biochemistry.
Groupe 2: T2D and established coronary artery disease; The presence of coronary artery disease (CAD) confirmed by coronary angiogram prior to the inclusion.; Patients with concomitant microvascular complications of diabetes will be excluded (nephropathy, retinopathy).
Groupe 3: Control, no T2D; Fasting glycemia <100 mg/dl and HbA1C <5.7%; Absence of a concomitant cardiovascular disease (CAD, stroke, PAD, neuropathy)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of EPCs dysregulation in Type 2 diabetes	Functional characterization of endothelial progenitor cells (EPCs) isolated from participants will be performed by assessing cellular signaling and functional pathways. Measurements will be compared among EPCs isolated from participants with type 2 diabetes and cardiovascular diseases, participants with type 2 diabetes without cardiovascular diseases, and healthy volunteers without diabetes or cardiovascular diseases.	Following the EPC isolation (15 - 20 days).
Functional Analysis of inflammatory responses in Endothelial Progenitor Cells in type 2 Diabetes with cardiovascular complications	Functional characterization of endothelial progenitor cells (EPCs) isolated from participants will be performed by assessing cellular signaling and functional pathways. Measurements will be compared among EPCs isolated from participants with type 2 diabetes and cardiovascular diseases, participants with type 2 diabetes without cardiovascular diseases, and healthy volunteers without diabetes or cardiovascular diseases.	Following the EPC isolation (15 - 20 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expression levels of angiocrine factor genes in EPCs	Expression levels of angiocrine related genes in EPCs measured by RNA sequencing and reported as normalized transcript counts.	Following the EPC isolation (15-20 days)
Cytosolic calcium concetration in EPCs	Cytosolic calcium concentration and expression of calcium signaling transcripts and proteins in EPCs assessed using functional calcium assays and molecular analyses.	Following the EPC isolation (15-20 days)
Quantification of Mitochondrial reactive oxygen species (ROS) levels in EPCs	Mitochondrial ROS production in EPCs measured using pre-designed fluorescence-based assay kits and reported as relative fluorescence units. Comparisons will be made among the three study groups.	Following the EPC isolation (15-20 days).
Protein Expression of Inflammatory Transcription Factors in Endothelial Progenitor Cells	Protein expression levels in lysates are quantified using western blot analysis and normalized to housekeeping proteins.	Following the EPC isolation (15 - 20 days).
Angiogenic Transcription Factor Expression in EPCs	Protein expression levels in lysates are quantified using western blot analysis and normalized to housekeeping proteins.	Time Frame: Following the EPC isolation (15 - 20 days).
Proportion of EPCs differentiating into endothelial cells in vitro	Differentiation of EPCs into adherent endothelial cells following culture in VEGF-, FGF-2-, IGF-1-, and heparin-supplemented media, assessed by endothelial morphology and marker expression.	14 days after initiation of in vitro differentiation.
Measurement of eNOS(endothelial nitric oxide synthase)-Dependent Nitric Oxide Production in Endothelial Progenitor Cells	eNOS(endothelial nitric oxide synthase) mRNA expression measured by RT-PCR and eNOS protein expression measured by western blotting in EPCs isolated from participants with type 2 diabetes and healthy volunteers.	Following EPC isolation (15-20 days) and 72 hours post-gene transfection.
Functional Outcomes of Genetically Enhanced Endothelial Progenitor Cells	eNOS mRNA expression measured by RT-PCR and eNOS protein expression measured by western blotting in EPCs isolated from participants with type 2 diabetes and healthy volunteers.	Following EPC isolation (15-20 days) and 72 hours post-gene transfection

Collaborators and Investigators

• Sponsor: Weill Cornell Medical College in Qatar
• Collaborators: Hamad Medical Corporation
• Investigators: Principal Investigator: Charbel Abi Khalil, MD,PhD, Weill Cornell Medicine-Qatar

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 13, 2026
• First Submitted That Met QC Criteria: April 21, 2026
• First Posted (Actual): April 29, 2026

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 18-00008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: ongoing discussion with the sponsor.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No