Jeremy Simpson

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Glucagon-like peptide-1 receptor (GLP-1R) agonists exert antihypertensive actions through incompletely understood mechanisms. Here we demonstrate that cardiac Glp1r expression is localized to cardiac atria and that GLP-1R activation promotes the secretion of atrial natriuretic peptide (ANP) and a reduction of blood pressure. Consistent with an indirect(More)
Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden death in children and young adults. Abnormalities in several signaling pathways are implicated in the pathogenesis of HCM, but the role of the RAS-RAF-MEK-ERK MAPK pathway has been controversial. Noonan syndrome (NS) is one of several autosomal-dominant conditions known as RASopathies, which are(More)
LIFEdb (http://www.LIFEdb.de) integrates data from large-scale functional genomics assays and manual cDNA annotation with bioinformatics gene expression and protein analysis. New features of LIFEdb include (i) an updated user interface with enhanced query capabilities, (ii) a configurable output table and the option to download search results in XML, (iii)(More)
BACKGROUND Cardiac troponins are modified during ischemic injury and are found as a heterogeneous mixture in blood of patients with cardiovascular diseases. We present a strategy to isolate cardiac troponins from human biological material, by use of affinity chromatography, and to provide samples ready for direct analysis by mass spectrometry. METHODS(More)
BACKGROUND Detection of skeletal muscle injury is hampered by a lack of commercially available assays for serum markers specific for skeletal muscle; serum concentrations of skeletal troponin I (sTnI) could meet this need. Moreover, because sTnI exists in 2 isoforms, slow (ssTnI) and fast (fsTnI), corresponding to slow- and fast-twitch muscles,(More)
Impaired muscle function (fatigue) may result, in part, from modification of contractile proteins due to inadequate O(2) delivery. We hypothesized that severe hypoxemia would modify skeletal troponin I (TnI) and T (TnT), two regulatory contractile proteins, in respiratory muscles. Severe isocapnic hypoxemia (arterial partial pressure of O(2) of(More)
BACKGROUND Microsomal prostaglandin E(2) synthase-1 (mPGES-1), encoded by the Ptges gene, catalyzes prostaglandin E(2) biosynthesis and is expressed by leukocytes, cardiac myocytes, and cardiac fibroblasts. Ptges(-/-) mice develop more left ventricle (LV) dilation, worse LV contractile function, and higher LV end-diastolic pressure than Ptges(+/+) mice(More)
KLF3 is a Krüppel family zinc finger transcription factor with widespread tissue expression and no previously known role in heart development. In a screen for dominant mutations affecting cardiovascular function in N-ethyl-N-nitrosourea (ENU) mutagenized mice, we identified a missense mutation in the Klf3 gene that caused aortic valvular stenosis and(More)
The purpose of this study was to determine if serum levels of skeletal troponin I (sTnI, fast and slow isoforms) could provide a sensitive marker of respiratory muscle damage in healthy humans subjected to inspiratory loads. To accomplish this, we studied healthy, young (27 ± 2 years, Mean ± SEM, n = 5) and middle-aged (55 ± 5, n = 5) men to (1) determine(More)
This study examined the role of pregnancy-induced changes in wakefulness (or non-chemoreflex) and central chemoreflex drives to breathe, acid-base balance and female sex hormones in the hyperventilation of human pregnancy. Thirty-five healthy women were studied in the third trimester (TM(3); 36.3+/-1.0 weeks gestation; mean+/-S.D.) and again 20.2+/-7.8(More)