Low-density lipoprotein receptor-related protein 1 (LRP1) expression in Mexican hypertensive patients
| ISRCTN | ISRCTN16657699 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16657699 |
| Secondary identifying numbers | JTRM-D-16-00728 |
- Submission date
- 09/11/2016
- Registration date
- 12/12/2016
- Last edited
- 24/04/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English summary of protocol
Background and study aims
Arterial hypertension (HTA) is high blood pressure in the vessels that carry blood from the heart to the body's tissues. It is a serious public health problem and is a major risk factor for cardiovascular (heart) disease, cerebrovascular disease (e.g., stroke) and kidney failure, which are major causes of death. Studies have found that there is a relationship between high blood pressure and atherosclerosis (the build-up of fatty material inside the arteries). This situation highlights the need to develop useful and easily accessible diagnostic tools for clinical practice. The intima/media thickness (IMT) is a measurement of the innermost two layers of carotid artery wall. It is an excellent marker for atherosclerosis and cardiovascular disease. The aims of this study are to compare the levels of LRP1 protein in circulating monocytes (white blood cells) from patients with high or normal blood pressure, to determine the relationship between LRP1 levels and IMT, and to find out whether LRP1 levels can be used as a marker for atherosclerosis.
Who can participate?
Mexicans age 40-70 with high or normal blood pressure
What does the study involve?
Participants’ body measurements are taken, including their height and weight, and their blood pressure is measured. Their IMT is measured with an ultrasound device. Blood samples are collected after fasting for 12 hours to measure LRP1 levels.
What are the possible benefits and risks of participating?
If a participant is found to have hypertension, increased IMT, high blood cholesterol and high LRP1 levels, they may have atherosclerosis. Knowing these results the doctor can give a preventive treatment to avoid cardiovascular and cerebrovascular disease. IMT is assessed with ultrasound, which does not expose the patient to any risk.
Where is the study run from?
National Institute of Cardiology "Ignacio Chavez" (Mexico)
When is the study starting and how long is it expected to run for?
October 2011 to July 2014
Who is funding the study?
National Council of Science and Technology (Mexico)
Who is the main contact?
Dr Claudia Huesca-Gomez
c_huesca@yahoo.com
Contact information
Scientific
Juan Badiano No 1
Col. Sección XVI
C.P.14080
México City
14080
Mexico
 ORCID ID |
0000-0002-6806-3484 |
|---|---|
| Phone | (52-55) 55 73 29 11 Ext.1278 |
| c_huesca@yahoo.com |
Study information
| Study design | Single-center observational case-control study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Case-control study |
| Study setting(s) | Hospital |
| Study type | Screening |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Monocyte low-density lipoprotein receptor-related protein 1 (LRP1) expression correlates with intima-media thickening in Mexican hypertensive patients |
| Study acronym | LRP1 hypertensive |
| Study objectives | Arterial hypertension, one of major risk factors for atherosclerosis, contributes to foam cell formation in the vasculature though low-density lipoprotein receptor-related protein 1 (LRP1) upregulation. The purpose of this work was to study the association between monocyte LRP1 mRNA expression and LRP1 protein levels and intima/media thickness in the carotid artery (IMT) of patients with essential hypertension If the LRP1 receptor modulates the uptake of c-LDL associated with hypertension, an increased IMT is expected to be found in hypertensive patients along with an overexpression of LRP1 in peripheral blood monocytes The aims of this study were: 1. To compare LRP1 expression levels in circulating monocytes from patients with essential hypertension against normotensive patients 2. To determine the relationship between LRP1 overexpression and arterial intima/media thickening to assess if monocyte LRP1 expression is a potential biomarker for atherosclerosis |
| Ethics approval(s) | Commission of bioethics of the INC Ignacio Chavez, 16/03/2010, ref: 10-665 |
| Health condition(s) or problem(s) studied | Arterial hypertension |
| Intervention | The population is recruited from the outpatient Service of the National Institute of Cardiology "Ignacio Chavez", where the hypertension diagnosis was made by a medical specialist. The subjects underwent anthropometric measurements determining their height in meters (m) weight in kilograms (kg). Blood pressure is measured using a mercury sphygmomanometer following the recommendations of the VII Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC VII). Systolic and diastolic blood pressures are measured after rest for at least 10 min, and the average of the second and third measurements is recorded for analysis. Hypertension is defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg or a previous clinical diagnosis of essential hypertension. A specialist in sonography resolution assesses the intima/media thickness in the carotid artery, all measurements are performed with a Sonosite Micromax ultrasound device coupled to a 13 MHz multifrequency high-resolution linear transducer. Blood samples were collected after a fasting period of 12 hours. Commercial enzymatic methods were used to determine circulating TC and TG, HDL-C, LDL-C. Angiotensin II was determined by capillary electrophoresis and C-reactive protein was determined by nephelometry. Peripheral blood mononuclear cell (PBMCs) are isolated from blood collected in EDTA using the Ficoll separation method. Total RNA was extracted using monocyte TripureTM isolation reagent (Roche Molecular Biochemicals) followed by a reverse transcription reaction. LRP1 gene expression and HPRT (endogenous gene) were quantified using a commercial kits "TaqMan Gene Expression" employing 7300 Real Time PCR System (Applied Biosystems) equipment. Total protein was extracted from monocytes using TriPureTM reagent (Roche Molecular Biochemicals). Membranes were incubated with monoclonal antibody against human LRP1 (85kDa β-chain). The QuantityOne program was used to quantify the bands present in the membranes. |
| Intervention type | Other |
| Primary outcome measure | 1. Blood pressure (normotensive or hypertensive), measured using a mercury sphygmomanometer at 10 months 2. LRP1 gene expression, quantified using a "TaqMan Gene Expression" commercial kit and 7300 Real Time PCR System at 3 months 3. LRP1 protein, analyzed by western blot at 6 months 4. The intima/media thickness in the carotid artery, assessed with a Sonosite Micromax ultrasound device coupled to a 13 MHz multifrequency high-resolution linear transducer at 10 months |
| Secondary outcome measures | N/A |
| Overall study start date | 01/10/2011 |
| Completion date | 25/07/2014 |
Eligibility
| Participant type(s) | Mixed |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 200 Mexican subjects (91 were normotensive and 109 were hypertensive) |
| Key inclusion criteria | Control group: 1. Normal pressure up to 120/80 mmHg 2. Mexican by birth, with at least two previous generations of Mexican origin 3. Agree to participate in the research protocol 4. Age 40-70 years Hypertensive group: 1. Blood pressure > 140/90mmHg 2. Mexican by birth, with at least two previous generations of Mexican origin 3. Agree to participate in the research protocol |
| Key exclusion criteria | Control group: 1. Have a history of cardiovascular disease 2. Have type 1 or 2 diabetes. 3. Have a chronic degenerative disease 4. Treatment with lipid-lowering medications Hypertensive group: 1. Treatment with lipid-lowering medications 2. Have type 1 or 2 diabetes 3. Have a chronic degenerative disease |
| Date of first enrolment | 24/07/2013 |
| Date of final enrolment | 27/02/2014 |
Locations
Countries of recruitment
- Mexico
Study participating centre
Col. Sección XVI, C.P.
México City
14080
Mexico
Sponsor information
Hospital/treatment centre
Juan Badiano No 1
Col. Sección XVI
C.P.14080
México City
14080
Mexico
| Phone | (52-55) 55 73 29 11 Ext.1278 |
|---|---|
| c_huesca@yahoo.com | |
"ROR" |
https://ror.org/046e90j34 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- Consejo Nacional de Ciencia y Tecnología, National Council of Humanities, Sciences and Technologies, Mexican National Council of Science and Technology, National Council for Science and Technology (CONACyT), National Council of Science and Technology, Mexico, Conahcyt
- Location
- Mexico
Results and Publications
| Intention to publish date | 21/01/2017 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | The results will be published in the first quarter of 2017. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available upon request from Dr Claudia Huesca-Gomez (c_huesca@yahoo.com). |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | 05/12/2016 | 24/04/2019 | No | No |
Additional files
- ISRCTN16657699_BasicResults_05Dec16.pdf
- uploaded 24/04/2019
Editorial Notes
24/04/2019: The basic results of this trial have been uploaded as an additional file.
