Ashmeetha Manilall

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• Doctor of Philosophy
• Researcher at University of the Witwatersrand

Background: The contribution of microRNAs remain poorly understood in the context of hypertensive cardiac pathology. Aim: The role of miR-146a-5p, miR-155-5p, and miR-29b-5p in cardiac hypertrophy and dysfunction was investigated in spontaneously hypertensive rats (SHR). Methods: Seven-month-old SHR (n=7 male, n=9 female), and normotensive Wistar K...

Systemic inflammation contributes to left ventricular (LV) dysfunction, however the role of the NLRP3 inflammasome in LV dysfunction in acute inflammatory conditions is unclear. This study investigated the role of the NLRP3 inflammasome in acute (24 h) cardiac structural and functional changes in vivo and in vitro in lipopolysaccharide (LPS)-induce...

Hypertension drives the development of concentric left ventricular hypertrophy (LVH). However, the relative contribution of pentraxin‐3 (PTX‐3), a novel marker for inflammatory cardiovascular disease, in the hypertrophic response to pressure overload has not been adequately elucidated. We investigated the role of PTX‐3 in the development of LVH in...

Background MicroRNAs have been implicated in the pathogenesis of cardiovascular disease. However, the contribution of microRNAs remain poorly understood in the context of hypertensive cardiac pathology. Aim We investigated the role of miR-146a-5p, -155-5p, and -29b-5p in the development of cardiac hypertrophy and dysfunction in male and female spo...

Nyaope is a highly addictive heroin derivative that elicits its effects via the -opioid receptor. Gene mutations and (cytosine-phospho-guanosine) CpG methylation, alter the function of the -opioid receptor gene (OPRM1) and protein. The single nucleotide polymorphisms (SNPs) rs1799971 (118 A>G) and intronic rs3778150 (T>C) in the OPRM1 have previous...

Nyaope is a local adulterated drug that contributes significantly to the psychosocial challenge of substance use in South Africa. Despite being a huge burden on society and the health care system, research into the deleterious effects of nyaope is limited. The aim of the present study was therefore to perform a chemical analysis of the drug and to...

Elevated systemic inflammation contributes to pathogenesis of heart failure with preserved ejection fraction (HFpEF), but molecular mechanisms are poorly understood. Although left ventricular (LV) diastolic dysfunction is the main cause of HFpEF, subclinical systolic dysfunction also contributes. We have previously shown that rats with collagen-ind...

Background Titin phosphorylation contributes to left ventricular (LV) diastolic dysfunction. The independent effects of inflammation on the molecular pathways that regulate titin phosphorylation are unclear. Methods We investigated the effects of collagen-induced inflammation and subsequent tumor necrosis factor-α (TNF-α) inhibition on mRNA expres...

Background Interleukin-6 (IL-6) receptor blockers improve systemic inflammation however, their inconsistent effects on lipid metabolism and drug-induced liver injuries warrant further investigation. This study aimed to determine the effects of IL-6 receptor blocker therapy on lipid metabolism and liver morphology in collagen-induced arthritis. Met...

Chronic inflammation causes dysregulated expression of microRNAs. Aberrant microRNA expression is associated with endothelial dysfunction. In this study we determined whether TNF-α inhibition impacted the expression of miRNA-146a-5p and miRNA-155-5p, and whether changes in the expression of these miRNAs were related to inflammation-induced changes...

Objective: To determine the mechanisms of inflammation-induced left ventricular (LV) remodeling and effects of blocking circulating tumor necrosis factor alpha (TNF-α) in a model of systemic inflammation. Methods: Seventy Sprague-Dawley rats were divided into three groups: the control group, the collagen-induced arthritis (CIA) group, and the an...

Objectives: To determine biologic disease-modifying anti-rheumatic drug effects on inflammation-induced cardiac geometry and function changes. Methods: Male and female Sprague-Dawley rats (n=92) were divided into four groups: control group, collagen-induced arthritis (CIA) group, anti-TNF-α group and anti-IL-6 group. Inflammation was induced by...

Background Normosmic congenital hypogonadotropic hypogonadism (ncHH) is caused by the deficient production, secretion, or action of gonadotropin‐releasing hormone (GnRH). Its typical clinical manifestation is delayed puberty and azoospermia. Homozygous and compound heterozygous mutations in the GNRHR gene (4q13.2) are the most frequent genetic caus...

Study question: Does the phenotype of women with normosmic congenital hypogonadotrophic hypogonadism (nCHH) and pituitary resistance to GnRH caused by biallelic mutations in the GnRH receptor (GNRHR) (nCHH/bi-GNRHR) differ from that of women with polycystic ovary syndrome (PCOS)? Summary answer: Women with nCHH/bi-GNRHR have variable pubertal de...

GnRH receptor mutations, Glu2.53(90)Lys and Glu2.53(90)Asp, cause congenital hypogonadotropic hypogonadism. The Glu2.53(90) side-chain has been proposed to form an intramolecular salt-bridge with Lys3.32(121), but conserved intramolecular interaction networks in G protein-coupled receptor crystal structures predict that it interacts with Ser3.35(12...

Gonadotropin-releasing hormone (GnRH) regulates reproduction. The human GnRH receptor lacks a cytoplasmic carboxy-terminal tail but has amino acid sequence motifs characteristic of rhodopsin-like, class A, G protein-coupled receptors (GPCRs). This review will consider how recent descriptions of X-ray crystallographic structures of GPCRs in inactive...