Browsing by Author "Kanthi, Yogendra"

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    At a crossroads: COVID-19 recovery and the risk of pulmonary vascular disease
    (Wolters Kluwer, 2021) Cascino, Thomas M.; Desai, Ankit A.; Kanthi, Yogendra; Medicine, School of Medicine
    Purpose of review: The coronavirus disease 2019 (COVID-19) pandemic has led to almost 3,000,000 deaths across 139 million people infected worldwide. Involvement of the pulmonary vasculature is considered a major driving force for morbidity and mortality. We set out to summarize current knowledge on the acute manifestations of pulmonary vascular disease (PVD) resulting from COVID-19 and prioritize long-term complications that may result in pulmonary hypertension (PH). Recent findings: Acute COVID-19 infection can result in widespread involvement of the pulmonary vasculature, myocardial injury, evidence of persistent lung disease, and venous thromboembolism. Post COVID-19 survivors frequently report ongoing symptoms and may be at risk for the spectrum of PH, including group 1 pulmonary arterial hypertension, group 2 PH due to left heart disease, group 3 PH due to lung disease and/or hypoxia, and group 4 chronic thromboembolic PH. Summary: The impact of COVID-19 on the pulmonary vasculature is central to determining disease severity. Although the long-term PVD manifestations of COVID-19 are currently uncertain, optimizing the care of risk factors for PH and monitoring for the development of PVD will be critical to reducing long-term morbidity and improving the health of survivors.
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    IL-18 mediates sickle cell cardiomyopathy and ventricular arrhythmias
    (American Society of Hematology, 2021) Gupta, Akash; Fei, Yu-Dong; Kim, Tae Yun; Xie, An; Batai, Ken; Greener, Ian; Tang, Haiyang; Ciftci-Yilmaz, Sultan; Juneman, Elizabeth; Indik, Julia H.; Shi, Guanbin; Christensen, Jared; Gupta, Geetanjali; Hillery, Cheryl; Kansal, Mayank M.; Parikh, Devang S.; Zhou, Tong; Yuan, Jason X-J; Kanthi, Yogendra; Bronk, Peter; Koren, Gideon; Kittles, Rick; Duarte, Julio D.; Garcia, Joe G. N.; Machado, Roberto F.; Dudley, Samuel C.; Choi, Bum-Rak; Desai, Ankit A.; Medicine, School of Medicine
    Previous reports indicate that IL18 is a novel candidate gene for diastolic dysfunction in sickle cell disease (SCD)-related cardiomyopathy. We hypothesize that interleukin-18 (IL-18) mediates the development of cardiomyopathy and ventricular tachycardia (VT) in SCD. Compared with control mice, a humanized mouse model of SCD exhibited increased cardiac fibrosis, prolonged duration of action potential, higher VT inducibility in vivo, higher cardiac NF-κB phosphorylation, and higher circulating IL-18 levels, as well as reduced voltage-gated potassium channel expression, which translates to reduced transient outward potassium current (Ito) in isolated cardiomyocytes. Administering IL-18 to isolated mouse hearts resulted in VT originating from the right ventricle and further reduced Ito in SCD mouse cardiomyocytes. Sustained IL-18 inhibition via IL-18-binding protein resulted in decreased cardiac fibrosis and NF-κB phosphorylation, improved diastolic function, normalized electrical remodeling, and attenuated IL-18-mediated VT in SCD mice. Patients with SCD and either myocardial fibrosis or increased QTc displayed greater IL18 gene expression in peripheral blood mononuclear cells (PBMCs), and QTc was strongly correlated with plasma IL-18 levels. PBMC-derived IL18 gene expression was increased in patients who did not survive compared with those who did. IL-18 is a mediator of sickle cell cardiomyopathy and VT in mice and a novel therapeutic target in patients at risk for sudden death.
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    Transcriptomic profiles in pulmonary arterial hypertension associate with disease severity and identify novel candidate genes
    (Sage, 2020-12-07) Romanoski, Casey E.; Qi, Xinshuai; Sangam, Shreya; Vanderpool, Rebecca R.; Stearman, Robert S.; Conklin, Austin; Gonzalez-Garay, Manuel; Rischard, Franz; Ayon, Ramon J.; Wang, Jian; Simonson, Tatum; Babicheva, Aleksandra; Shi, Yinan; Tang, Haiyang; Makino, Ayako; Kanthi, Yogendra; Geraci, Mark W.; Garcia, Joe G.N.; Yuan, Jason X.-J.; Desai, Ankit A.; Medicine, School of Medicine
    Using RNAseq, we identified a 61 gene-based circulating transcriptomic profile most correlated with four indices of pulmonary arterial hypertension severity. In an independent dataset, 13/61 (21%) genes were differentially expressed in lung tissues of pulmonary arterial hypertension cases versus controls, highlighting potentially novel candidate genes involved in pulmonary arterial hypertension development.