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Endovascular Health and Platelet Activity in Psoriasis

Award Number: K23HL152013
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 02/15/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2026

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Endovascular Health and Platelet Activity in Psoriasis - PROJECT SUMMARY/ABSTRACT Background: Psoriasis is a common chronic inflammatory skin disease associated with an ~50% increased risk of cardiovascular disease (CVD) compared to matched controls. The influence of psoriasis-related systemic inflammation on vascular health and subsequent cardiovascular (CV) risk is not fully known. Vascular endothelial dysfunction, activated platelets, and the interaction between the two are instrumental to the pathogenesis of atherosclerosis. As a way to understand mechanisms of increased CV risk in psoriasis, this study will test the overarching hypothesis that the vascular endothelium in psoriasis is inflamed, dysfunctional, and contributes to CVD development as assessed by endovascular and platelet phenotyping, and that platelets from patients with psoriasis act as effector cells promoting impaired vascular health. To develop therapeutic targets to reduce CV risk, mechanism(s) that lead to the development of clinical CVD must be clarified. Preliminary Data: Our group has shown using direct brachial vein endothelial cell analysis, that patients with psoriasis exhibit impaired vascular endothelial health. Furthermore, unbiased analysis highlights inflammasome (IL-1β) signaling with downstream IL-6 protein production as the highest differentially expressed systemic pathway in psoriasis and correlated with impaired endothelial vascular health. Our preliminary data also reveal that patients with psoriasis overexpress P-selectin (a marker of platelet activation), directly activate cultured human aortic endothelial cells in vitro, and that markers of platelet activation correlate with serum IL-6 levels. This suggests that platelets contribute to the impaired vascular health we observe in psoriasis. These findings have clinical implications because randomized clinical trials targeting the inflammasome pathway (with a corresponding circulating IL-6 reduction) in patients with established CVD reduced cardiac events. Methods: We will recruit 100 psoriasis and 50 healthy age-, sex-, race/ethnicity matched controls across the spectrum of psoriatic disease and various treatment modalities to explore: (1) Vascular health in vivo by flow- mediated brachial artery reactivity testing and pulse wave velocity studies, and directly ex vivo via analysis of endothelial cells obtained from brachial veins; (2) Platelet biology through investigations into platelet reactivity, platelet aggregation, and the platelets ability to activate endothelial cells in vitro. Objectives and Career Development: No study has shown that targeting psoriatic disease activity reduces the development of CVD. This proposal uses a highly collaborative environment between experts in CV and platelet biology, immunology, dermatology, and rheumatology. It will lay the groundwork to propose future larger-scale studies designed to reduce CV risk in patients with psoriasis. Furthermore, it will allow the PI to become an expert in pro-inflammatory conditions, refine innovative methodologies and laboratory techniques to study mechanisms of subclinical CVD, and provide a framework to become an independent clinical- translational investigator.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $171,789 )
2025	2025	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Cardiovascular Diseases Research	000	5	1/15/2025	NON-COMPETING CONTINUATION	$171,789
														Subtotal = $171,789

Issue Date FY: 2024 ( Subtotal = $172,424 )
2024	2024	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Cardiovascular Diseases Research	000	4	1/12/2024	NON-COMPETING CONTINUATION	$172,424
														Subtotal = $172,424

Issue Date FY: 2023 ( Subtotal = $173,044 )
2023	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Cardiovascular Diseases Research	000	3	2/9/2023	NON-COMPETING CONTINUATION	$173,044
														Subtotal = $173,044

Issue Date FY: 2022 ( Subtotal = $173,646 )
2022	2022	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Cardiovascular Diseases Research	000	2	1/21/2022	NON-COMPETING CONTINUATION	$173,646
														Subtotal = $173,646

Issue Date FY: 2021 ( Subtotal = $174,229 )
2021	2021	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Cardiovascular Diseases Research	000	1	2/15/2021	NEW	$174,229
														Subtotal = $174,229

Grand Total All Awards = $865,132

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Endovascular Health and Platelet Activity in Psoriasis

Award Number: K23HL152013

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 02/15/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2026

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