Osman Ahmed

Karolinska Institutet | KI · Department of Medicine, Solna

Background: The liver is an important immunological organ and liver inflammation is part of the pathophysiology of non-alcoholic steatohepatitis, a condition that may promote cirrhosis, liver cancer, liver failure, and cardiovascular disease. Despite dense innervation of the liver parenchyma, little is known about neural regulation of liver functi...

Endothelial dysfunction and impaired vasodilation are linked with adverse cardiovascular events. T lymphocytes expressing choline acetyltransferase (ChAT), the enzyme catalyzing biosynthesis of the vasorelaxant acetylcholine (ACh), regulate vasodilation and are integral to the cholinergic antiinflammatory pathway in an inflammatory reflex in mice....

Apolipoprotein-B (APOB) containing lipoproteins are causative for atherosclerotic cardiovascular disease. Whether the vasculature is the initial responding site or if atherogenic-dyslipidemia effects other organs simultaneously is unknown. We set out to discover how the liver responds to a dyslipidemic insult through the creation of inducible mouse...

Background Sterol O-Acyltransferase 2 (Soat2) encodes acyl-Coenzyme A:cholesterol acyltransferase 2 (ACAT2), which synthesizes cholesteryl esters in hepatocytes and enterocytes fated either to storage or to secretion into nascent triglyceride-rich lipoproteins. Objectives We aimed to unravel the molecular mechanisms leading to reduced hepatic stea...

Introduction and Hypothesis: PCSK9-inhibition reduces the residual cardiovascular risk associated with LDL-cholesterol (LDL-C), but the wide-spread use of the antibody-based therapies is affected by the costs, especially in low- and middle-income countries. Hence, there is a need to identify affordable and effective drugs to inhibit PCSK9. Methods:...

Aim: Recent reports show an association between statins therapy and reduction in 28-day all-cause mortality among Coronavirus disease 2019 (COVID-19) patients. This association is poorly understood mechanistically. Hence, we investigated whether simvastatin regulates hepatic expression of genes involved in humoral and innate immune responses, and i...

The determination of the lipid content in liver offers the potential to investigate metabolic alterations in different research contexts. Here, we describe a method to determine cholesterol, triglycerides, and phospholipids in liver samples based on total lipid isolation by a 2:1 chloroform–methanol mixture (Folch extraction) and specific enzymatic...

The response to overfeeding is sex dependent, and metabolic syndrome is more likely associated to obesity in men or postmenopausal women than in young fertile women. We hypothesized that obesity-induced metabolic syndrome is sex dependent due to a sex-specific regulation of the fatty acid (FA) synthesis pathways in liver and white adipose depots. W...

The liver is the central organ for lipid, lipoprotein and glucose homeostasis, thus hepatic metabolic disturbances can predispose individuals to develop cardiometabolic disorders (CMD) such as atherosclerotic cardiovascular diseases (ASCVD), type 2 diabetes mellitus (T2DM), and nonalcoholic fatty liver disease (NAFLD).The overall aim of this thesis...

Obesity triggers the development of non-alcoholic fatty liver disease (NAFLD), which involves alterations of regulatory transcription networks and epigenomes in hepatocytes. Here we demonstrate that G protein pathway suppressor 2 (GPS2), a subunit of the nuclear receptor corepressor (NCOR) and histone deacetylase 3 (HDAC3) complex, has a central ro...

Background In randomized trials (SHARP [Study of Heart and Renal Protection], IMPROVE‐IT [Improved Reduction of Outcomes: Vytorin Efficacy International Trial]), combination of statin and ezetimibe resulted in additional reduction of cardiovascular events. The reduction was greater in patients with type 2 diabetes mellitus (T2DM), where elevated re...

Data S1. Supplemental methods. Table S1. Lipid Contribution in Lipoprotein Fractions Used in Figure 2 Table S2. Contribution of Different Subclasses for Their Respective Fraction Baseline Table S3. Correlation of Percentage Changes of Proteoglycan (PG) Binding and Lipoprotein Particle Number and Composition Table S4. Safety Assessment Analyses

Depletion of the cholesterol esterifying enzyme acyl-Coenzyme A: cholesterol acyltransferase 2 (ACAT2, encoded by Soat2) protects mice from atherosclerosis, diet-induced hypercholesterolemia, and hepatic steatosis when fed high-cholesterol diet. The glucose transporter 2 (GLUT2) represents the main gate of glucose uptake by the liver. Lipid synthes...

Simvastatin and ezetimibe reduce plasma lipoprotein binding to human arterial proteoglycans in gallstone diseased patients. Ahmed O1,2#, Littmann K1#, Gustafsson U3, Pramfalk C1,4, Öörni K5, Larsson L1, Sahlin S3, Camejo G1, Parini P1,4,6, Eriksson M6 1 Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Sto...

Background and aims: Transforming growth factor β induced factor homeobox 1 (TGIF1) is a transcriptional repressor that limits the response to transforming growth factor ß signaling and also represses transcription independent of this pathway. Recently, we found higher serum cholesterol levels and more hepatic lipid accumulation in mice lacking Tg...

Introduction: Large genetic studies have recently recognized remnant-cholesterol, defined as cholesterol in triglyceride (TG)-rich lipoproteins, as a causal risk factor for ischemic heart disease and low grade inflammation, independently of HDL-cholesterol. NPC1L1 in the intestine is the target of ezetimibe, but its function in the liver is still u...

Background Visceral leishmaniasis (VL), caused by protozoa of the Leishmania donovani complex, is a widespread parasitic disease of great public health importance; without effective chemotherapy symptomatic VL is usually fatal. Distinction of asymptomatic carriage from progressive disease and the prediction of relapse following treatment are hamper...

BACKGROUND: Visceral leishmaniasis (VL), a widely distributed systemic disease caused by infection with the Leishmania donovani complex (L. donovani and L. infantum), is almost always fatal if symptomatic and untreated. A rapid point-of-care diagnostic test for anti-Leishmania antibodies, the rK39-immunochromatographic test (rK39-ICT), has high sen...

The liver X receptors (LXR)α and LXRβ are transcription factors belonging to the nuclear receptor family which play a central role in metabolic homeostasis being master regulators of key target genes in the glucose and lipid pathways. Wild-type (Wt), LXRα(-/-) and LXRβ(-/-) mice were fed a chow diet with (treated) or without (control) the synthetic...

Background. Poor access to diagnosis stymies control of visceral leishmaniasis (VL). Antibody-detecting rapid diagnostic tests (RDTs) can be performed in peripheral health settings. However, there are many brands available and published reports of variable accuracy. Methods. Commercial VL RDTs containing bound rK39 or rKE16 antigen were evaluated...

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The Leishmania OligoC-TesT and NASBA-Oligochromatography (OC) were recently developed for simplified and standardised molecular detection of Leishmania parasites in clinical specimens. We here present the phase II evaluation of both tests for diagnosis of visceral leishmaniasis (VL), cutaneous leishmaniasis (CL) and post kala-azar dermal leishmania...