Biomarkers of CVD Dysfunction in Hypertensive Disorders of Pregnancy

NCT05806372 | Unknown

• 1 other identifier: RC 29/22
• Study Type: observational
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

Profound and concomitant cardiovascular hemodynamic changes, necessary to support fetoplacental development and its increasing supply demands, occur during a physiological pregnancy characterized by an increase in cardiac output, heart rate and plasma volume, and fall in vascular resistance and blood pressure. The result of these changes is a volume overload that will lead to a compensatory transient left ventricular eccentric hypertrophy. This, together with the pro-inflammatory state typical of pregnancy, represents the pregnancy as a stress-test for the maternal cardiovascular system. Pregnancies complicated by hypertensive disorders of pregnancy (HDP), particularly those with early onset and/or complicated by intrauterine fetal growth restriction (FGR), are characterized by a cardiovascular maladaptation. Women who experienced HDP in pregnancy, especially pre-eclampsia (PE), more often develop later in life ischemic heart disease, hypertension and stroke, obesity, dyslipidemia, and end-stage renal disease. Regardless its clinical impact, very little knowledge is available on the mechanisms by which PE could lead to cardiovascular disease (CVD), and, especially, to heart failure after pregnancy. Preliminary results suggest a cross-talk between pregnancy-induced biomarkers and cardio-vascular system. Particularly, cultures of neonatal rat cardiomyocytes and fibroblasts were used to investigate the role of the serum of women with HDP in regulating their proliferation. 5-ethynyl-2'-deoxyuridine (EdU) was administered to label DNA synthesis in proliferating cells. After 3 days of in vitro culture, EdU incorporation was analyzed upon immunofluorescence staining using specific antibodies by high content microscopy. A possible protective effect exerted by the selected sera against apoptosis was evaluated, as well, by Caspase activation. Moreover, the effect of cardiomyocytes and fibroblasts proliferation and apoptosis on maternal hemodynamic parameters was evaluated using median regression models. These data show that the serum of women with HDP triggers a net increase in the percentage of proliferating cardiomyocytes compared to controls. Moreover, there were relationship between cardiomyocytes and fibroblasts proliferation and maternal hemodynamics parameters thus, supporting the hypothesis that the serum of women with HDP may contain factors capable of stimulating cardiac cells in response to the cardiovascular stress-test

Conditions

Cardiovascular Diseases; Pregnancy

Keywords

Cardiomyocytes; microRNA,; hypertensive disorders of pregnancy

Outcome Measures

Primary Outcomes (2)

• Number of biomarkers predicting cardiomyocyte hypertrophy and fibroblast proliferation

  By exploiting the availability of a library of viral vectors encoding for the whole secretome (about 1200 secreted proteins) and the whole miRNAome (about 2000 human microRNAs) a high throughput screening will be carried out to identify molecules able to control the viability, proliferation and cell size of both primary cardiomyocytes and cardiac fibroblasts. Data mining methods for multi-target prediction, such as ensembles of predictive clustering trees, will be used to correlate multiple independent variables (e.g., potential biomarkers) to the multiple clinical outcomes (indices of cardio-vascular dysfunction measured by echocardiography).

  During pregnancy, at the time of HDP diagnosis

• Number of biomarkers predicting cardiomyocyte hypertrophy and fibroblast proliferation

  By exploiting the availability of a library of viral vectors encoding for the whole secretome (about 1200 secreted proteins) and the whole miRNAome (about 2000 human microRNAs) a high throughput screening will be carried out to identify molecules able to control the viability, proliferation and cell size of both primary cardiomyocytes and cardiac fibroblasts. Data mining methods for multi-target prediction, such as ensembles of predictive clustering trees, will be used to correlate multiple independent variables (e.g., potential biomarkers) to the multiple clinical outcomes (indices of cardio-vascular dysfunction measured by echocardiography).

  24 months post-partum

Study Arms (3)

HDP with FGR

Evaluation of sera and ultrasound data on fetal growth and Doppler velocimetry in women with HDP and fetal growth restriction.

HDP without FGR

Evaluation of sera and ultrasound data on fetal growth and Doppler velocimetry in women with HDP and without fetal growth restriction.

Normotensive

Evaluation of sera and ultrasound data on fetal growth and Doppler velocimetry in normotensive women.

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: Pregnant women
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Singleton pregnant women between 24 and 40 gestational weeks with HDP (with and without fetal growth disorder) and normotensive (controls)

You may qualify if:

• CASES:
• Pregnant women affected by HDP
• Women ≥18 years old
• Women able to give an informed consent
• CONTROLS
• Uneventful pregnancy of women ≥18 years old
• Women able to give an informed consent

You may not qualify if:

• No informed consent
• Women \<18 years old
• Presence of other maternal pathologies as viral disease, diabetes
• Fetal chromosomal/structural anomalies

Sponsors & Collaborators

• IRCCS Burlo Garofolo: lead

Study Sites (1)

IRCCS Burlo Garofolo

Trieste, 34137, Italy

Location

Biospecimen

Retention: SAMPLES WITH DNA

sera of women that experienced HDP with and without FGR will be used

MeSH Terms

Conditions

Cardiovascular Diseases

Study Officials

• Tamara Stampalija, MD

  IRCCS materno infantile Burlo Garofolo

  STUDY DIRECTOR

Central Study Contacts

Tamara Stampalija, MD

CONTACT

+390403785486; tamara.stampalija@burlo.trieste.it

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2023
• First Posted: April 10, 2023
• Study Start: October 15, 2023
• Primary Completion: March 15, 2025
• Study Completion: March 15, 2025
• Last Updated: August 24, 2023

Record last verified: 2023-08

Locations

IT (1)