Gut Inflammation, Hypertension
Conditions
Brief summary
The study compared basic properties of gut epithelia of hypertensive and normotensive reference subjects. The study determined if there are fundamental differences in the gut epithelium in hypertension compared to normotension. Specifically, this study examined gene expression profiles of gut organoids derived from biopsy samples of hypertensive and normotensive individuals undergoing clinically indicated colonoscopy.
Detailed description
This investigated whether there is a difference in gut epithelia between individuals with and without high blood pressure by comparing colonic biopsy samples from. The study was conducted among adults undergoing routine elective colonoscopy at the University of Florida. Participants were classified into high blood pressure (HBP) and normotensive (REF) groups based on blood pressure criteria defined by the 2017 ACC/AHA guidelines. The study had two primary aims. Aim 1 was to evaluate whether gene expression patterns in the gut epithelium differ between hypertensive and normotensive individuals using RNA sequencing. Aim 2 was to assess whether gut organoids-three-dimensional epithelial cultures derived from colonic biopsies-exhibit different growth rates and proportions, using immunohistochemistry and fluorescence-activated cell sorting (FACS). Biopsy specimens were collected during clinically indicated colonoscopies. Tissue samples were processed immediately after collection: one portion was snap-frozen for RNA isolation and sequencing; the other was used to establish gut organoid cultures. Data were coded and stored in a secure, encrypted database with all identifiers removed to protect confidentiality, in compliance with HIPAA regulations. Although the study protocol initially planned to recruit 60 participants, a total of 35 subjects were successfully enrolled-16 with high blood pressure (HBP) and 19 normotensive (REF) participants. All provided adequate biopsy material for gene expression analysis.
Interventions
OTHERGene Expression
Gene expression analysis of biopsy specimens obtained during routine colonoscopy examination
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of Florida
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Inclusion/
Exclusion criteria
for hypertension participants * Ages: 18-80 years old with a weight greater than or equal to 110 lbs * Diagnosis of hypertension or without hypertension for the reference cohort. 2017 ACC/AHA (American College of Cardiology/American Heart Association) definition for hypertension (systolic blood pressure ≥130 mmHg and/or diastolic BP ≥80 mmHg) will be used. * Scheduled elective colonoscopy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Differential Gene Expression in Gut Epithelium | At time of colonoscopy (single visit) | Number of differentially expressed genes identified through RNA sequencing of colonic epithelial tissue obtained during colonoscopy. Expression profiles were compared between individuals with High Blood pressure (HBP) (hypertensive group) and normotensive reference (REF) participants. Genes were considered differentially expressed if they met criteria of false discovery rate (FDR)-adjusted p-value \< 0.05 and absolute fold change ≥ 1.5. |
| Growth Rates of Gut Organoids | Within days to weeks post-biopsy (in vitro culture period) | To compare growth rates and proportions of gut organoids derived from High Blood pressure (HBP) vs. normotensive (REF) participants. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hypertensive Group Participants were adults undergoing routine screening colonoscopy who met study eligibility criteria and provided written informed consent. Based on their blood pressure status, participants were categorized as individuals with high blood pressure (hypertensive group), defined according to the 2017 ACC/AHA guidelines
Gene Expression: Gene expression analysis of biopsy specimens obtained during routine colonoscopy examination | 16 |
| Normotensive Group Participants were adults undergoing routine screening colonoscopy who met study eligibility criteria and provided written informed consent. Based on their blood pressure status, participants were categorized as individuals without hypertension (normotensive group), defined according to the 2017 ACC/AHA guidelines | 19 |
| Total | 35 |
Baseline characteristics
| Characteristic | Hypertensive Group | Total | Normotensive Group |
|---|---|---|---|
| Age, Continuous | 62 Years | 58 Years | 55 Years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) White | 11 Participants | 24 Participants | 13 Participants |
| Region of Enrollment United States | 16 Participants | 35 Participants | 19 Participants |
| Sex: Female, Male Female | 10 Participants | 25 Participants | 15 Participants |
| Sex: Female, Male Male | 6 Participants | 10 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 19 |
| other Total, other adverse events | 0 / 16 | 0 / 19 |
| serious Total, serious adverse events | 0 / 16 | 0 / 19 |
Outcome results
Primary
Differential Gene Expression in Gut Epithelium
Number of differentially expressed genes identified through RNA sequencing of colonic epithelial tissue obtained during colonoscopy. Expression profiles were compared between individuals with High Blood pressure (HBP) (hypertensive group) and normotensive reference (REF) participants. Genes were considered differentially expressed if they met criteria of false discovery rate (FDR)-adjusted p-value \< 0.05 and absolute fold change ≥ 1.5.
Time frame: At time of colonoscopy (single visit)
Population: Colonic biopsies from HBP participants revealed 35 differentially expressed genes (29 upregulated, 6 downregulated) compared to normotensive subjects (reference group).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Study Participants | Differential Gene Expression in Gut Epithelium | Upregulated Genes | 29 Differentially expressed gene |
| All Study Participants | Differential Gene Expression in Gut Epithelium | Downregulated Genes | 6 Differentially expressed gene |
Primary
Growth Rates of Gut Organoids
To compare growth rates and proportions of gut organoids derived from High Blood pressure (HBP) vs. normotensive (REF) participants.
Time frame: Within days to weeks post-biopsy (in vitro culture period)
Population: No data obtained for this outcome measure because organoid preparations did not meet feasibility criteria for sample quantity and quality required for FACS and IHC. Further samples will never be obtained.