权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Advanced CV imaging and immunophenotyping to study coronary vascular health in psoriasis

先进的 CV 成像和免疫表型研究银屑病冠状血管健康

基本信息

批准号：
10459556
负责人：
Brittany nicole Weber
金额：
$ 19.19万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10459556
关键词：
Address Advisory Committees Affect Aftercare Age Anti-Inflammatory Agents Atherosclerosis Award Blood Vessels Blood flow Cardiac Cardiovascular Diseases Cardiovascular system Cells Cellular biology Cessation of life Clinical Clinical Trials Coronary Coronary Arteriosclerosis Data Dermatology Development Disease Echocardiography Endothelium Epitopes Event Exposure to FDA approved Foundations Functional Imaging Functional disorder Funding Future Goals Health Heart failure Heterogeneity High Prevalence Imaging Techniques Immune Immunologist Immunology Immunophenotyping Impairment Inflammation Inflammatory Interleukin-17 Investigation Left Ventricular Function Link Measures Mechanics Mediating Mediator of activation protein Medicine Mentors Methods Microvascular Dysfunction Molecular Profiling Monitor Morphology Myocardial Myocardial Infarction Myocardial Ischemia Myocardial dysfunction Myocardial tissue Outcome Pathway interactions Patients Perfusion Peripheral Blood Mononuclear Cell Physicians Play Population Population Control Positron-Emission Tomography Prevalence Prevention strategy Prognosis Program Development Psoriasis Psoriatic Arthritis Relaxation Research Research Personnel Rheumatology Risk Risk Factors Role Scientist Severity of illness Solid Stress Structure Symptoms Techniques Testing Therapeutic Trials Tissues Training Translations Vascular Diseases Vasodilator Agents Vasomotor base cardiometabolic risk cardiometabolism cardiovascular disorder risk cardiovascular imaging cardiovascular risk factor career career development chronic inflammatory skin clinical care clinical risk clinical translation design endothelial dysfunction functional improvement genetic signature heart imaging improved indexing insight interleukin-23 mortality multimodality novel patient population prevent response sex risk single cell analysis single-cell RNA sequencing skills skin disorder systemic inflammatory response transcriptome transcriptome sequencing

项目摘要

Project Summary/Abstract Psoriasis is highly linked to cardiovascular disease (CVD), including myocardial infarction (MI), heart failure and CV mortality. An increased prevalence of CV risk factors in these patients only partially accounts for this enhanced clinical risk. Although systemic inflammation is thought to be a key mediator of the onset and progression of these cardiometabolic abnormalities, the excess CV risk conferred by psoriatic disease remains understudied. We will use novel multi-modality cardiac imaging to quantify abnormalities in vascular health, and cardiac structure and function and assess the association with cellular immunophenotype. The central hypothesis of this study is that reducing inflammation with tildrakizumab, an FDA approved therapy for psoriasis that inhibits the IL-23 and Th17 pathway of inflammation, will quantitatively improve myocardial blood flow and coronary flow reserve (CFR) as measured by positron emission tomography (PET) over 6 months in patients with moderate-severe psoriasis disease and enhanced CV risk. In so doing, improvement in coronary vasoreactivity, endothelial function, and tissue perfusion may have beneficial effects on myocardial mechanics, and ultimately, symptoms and prognosis. We propose to use two state-of-the-art techniques, quantitative perfusion PET imaging and cellular immunophenotyping by single cell analysis [single cell RNA-seq, cellular indexing of transcriptomes and epitopes (CITE)-seq] of peripheral blood mononuclear cells, combined with echocardiography. In Specific Aim 1, we will evaluate whether tildrakizumab therapy will (1) improve coronary vascular function based on CFR, (2) improve myocardial mechanics, and (3) whether this functional improvement will be correlated with the change in CFR after 6 months of treatment. In Specific Aim 2, we will evaluate the relationship between cellular immunophenotype and coronary vasomotor dysfunction and myocardial mechanics, at baseline and after therapy with tildrakizumab for 6 months. The overarching goal of this proposal is to use physiologic imaging techniques already available as part of routine clinical care, and novel cellular immunophenotyping to investigate mechanisms linking psoriatic disease and inflammation to coronary vascular health and cardiac structure and function. This study will address an unmet and needed clinical translation in psoriatic disease. This research will be accomplished in the setting of a comprehensive career development program designed to provide the candidate, an early career investigator with training in CV medicine and CV imaging, with the skills needed to become an independent physician-scientist in CV medicine. Her long-term career goal is to be an independent scientific investigator, integrating immunology with cardiovascular imaging to better define the role of systemic inflammation in cardiovascular pathophysiology, and ultimately inform future therapeutic trials. An outstanding mentoring team and advisory committee of established scientists in the fields of CV medicine, CV imaging, Rheumatology, Dermatology, Immunology, and cellular biology will guide the candidate in her transition to scientific independence over the course of the award period.

项目总结/文摘