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Benzene Exposure and Heart Failure

Award Number: R21ES033334
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Benzene Exposure and Heart Failure - Project Summary Long-term exposure air pollutant exposure is recognized as a risk factor for cardiovascular diseases including myocardial ischemia and heart failure. Recent epidemiological and experimental data indicate that many volatile organic compounds including benzene contribute to worsening outcomes in patients with progressive heart disease. Benzene is the most abundant air pollutant mostly generated from automobile exhaust and tobacco smoke. Despite high prevalence of benzene in air-pollutants, little is known about the direct effects of inhaled benzene on heart failure morbidity and mortality in well-controlled animal studies. Our recent studies show that benzene exposure resembling moderate to high levels of human exposure worsens cardiac function in pressure overload-induced mice. The benzene-induced worsening of cardiac functions was accompanied by endothelial activation and infiltration of granulocytes in the heart and upregulation of gene expression for CXCL1 chemokine and alarmin S100A8/A9 complex which promotes neutrophil and monocyte chemotaxis and adhesion through TLR4 and RAGE signaling. Our new preliminary data show that ambient benzene exposure causes endothelial activation/injury in humans and chronic low dose exposure stimulates endothelial activation/injury in mice. Using animal model of pressure overload-induced cardiac dysfunction, we will examine the effects of environmental benzene exposure on cardiac dysfunction (echocardiography, cardiac hypertrophy, analysis of composition and activation status of infiltrating immune cells) during heart remodeling (Aim 1), and examine the molecular mechanisms by which benzene exacerbate cardiac dysfunction (Aim 2). Successful completion of these studies will, for the first time, show how benzene affect cardiac function in patients with progressing heart failure and provide mechanistic insight into this process.


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: 2026 ( Subtotal = -$2,335 )
2026	2023	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Environmental Health	000	2	11/21/2025	NON-COMPETING CONTINUATION	-$2,335
														Subtotal = -$2,335

Issue Date FY: 2023 ( Subtotal = $195,625 )
2023	2023	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Environmental Health	000	2	6/29/2023	NON-COMPETING CONTINUATION	$195,625
														Subtotal = $195,625

Issue Date FY: 2022 ( Subtotal = $234,750 )
2022	2022	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Environmental Health	000	1	6/23/2022	NEW	$234,750
														Subtotal = $234,750

Grand Total All Awards = $428,040

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Benzene Exposure and Heart Failure

Award Number: R21ES033334

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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