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CTP Supplement to Parent Grant: The Role of Histone Deacetylase 9 in Vascular Calcification

Principal Investigator: Rajeev Malhotra

Funding Mechanism: National Institutes of Health – Grant

ID number: 3R01HL142809-03S1

Award Date: 7/17/2020

Institution: Massachusetts General Hospital

In this CTP Supplement to a parent grant studying the role of histone deacetylase 9 (HDAC9, an essential regulator of vascular function), researchers will investigate whether toxic metals from vaping products prompt HDAC9-dependent dysregulation of vascular cell function and increased inflammation. Study aims are: (1) to analyze the heavy metal profiles of aerosol vapor generated by different open-system vaping devices, and (2) to determine the effects of toxic heavy metals in vaping aerosols and e-fluids on vascular cell function in vitro and cardiovascular and pulmonary function in vivo. To achieve Aim 1, researchers will use mass spectrometry to profile metals (by element and concentration) in aerosol vapor from six different open-system vaping devices (three refillable cartridges and three tank devices) and identify the origin (e-fluid, reservoir, heating coil) of each metal. To achieve Aim 2, researchers will use cell culture-based assays to determine how vaping aerosols, e-fluids, and metal constituents identified in Aim 1 affect gene and protein expression patterns and cellular function. They will also use wild-type and HDAC9-deficient mice to study the effects of chronic (1 month) vaping aerosol exposure on cardiovascular function (echocardiography), blood pressure, endothelial function, vascular reactivity, pulmonary function, and inflammation profile. Study findings may inform regulatory activities related to e-cigarettes. 

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