A5023808107- Neuroscience of respiration and sleep
- Metabolism, Diabetes, and Cancer
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Cancer, Hypoxia, and Metabolism
- RNA Research and Splicing
- Respiratory Support and Mechanisms
- High Altitude and Hypoxia
- Diet, Metabolism, and Disease
- Nitric Oxide and Endothelin Effects
- Pancreatic function and diabetes
- Circular RNAs in diseases
- Mitochondrial Function and Pathology
- Heme Oxygenase-1 and Carbon Monoxide
- Pregnancy and preeclampsia studies
- Pulmonary Hypertension Research and Treatments
- Adipose Tissue and Metabolism
- Birth, Development, and Health
- Gestational Diabetes Research and Management
University of Edinburgh
2010-2022
The Queen's Medical Research Institute
2019-2021
In response to blood vessel wall injury, aberrant proliferation of vascular smooth muscle cells (SMCs) causes pathological remodeling. However, the controlling mechanisms are not completely understood.
[Figure: see text].
Long noncoding RNAs (lncRNAs) are an emergent class of molecules with diverse functional roles, widely expressed in human physiology and disease. Although some lncRNAs have been identified cardiovascular disease, their potential as novel targets the prevention atherosclerosis is unknown. We set out to discover important unstable plaque gain insight into relevance. Approach Results: Analysis RNA sequencing previously performed on stable atherosclerotic a panel 47 differentially regulated...
Key points Uterine artery vasodilatation is a key mechanism for increasing utero‐placental blood flow and fetal nutrient supply. Since the pioneering work of Joseph Barcroft, natural laboratory high altitude has been used to study mechanisms regulating uterine supply growth. Genes near metabolic sensor adenosine monophosphate‐activated protein kinase (AMPK) have implicated in genetic protection from altitude‐associated growth restriction. We show that AMPK present tissues vasodilator effects...
Modulation of breathing by hypoxia accommodates variations in oxygen demand and supply during, for example, sleep ascent to altitude, but the precise molecular mechanisms this phenomenon remain controversial. Among genes influenced natural selection high-altitude populations is one adenosine monophosphate-activated protein kinase (AMPK) α1-catalytic subunit, which governs cell-autonomous adaptations during metabolic stress.We investigated whether AMPK-α1 and/or AMPK-α2 are required hypoxic...
Key points Progression of hypoxic pulmonary hypertension is thought to be due, in part, suppression voltage‐gated potassium channels (K v ) arterial smooth muscle by hypoxia, although the precise molecular mechanisms have been unclear. AMP‐activated protein kinase (AMPK) has proposed couple inhibition mitochondrial metabolism hypoxia acute vasoconstriction and progression hypertension. Inhibition complex I electron transport chain activated AMPK inhibited K 1.5 myocytes. activation...
Abstract The hypoxic ventilatory response (HVR) is critical to breathing and thus oxygen supply the body primarily mediated by carotid bodies. Here we reveal that afferent discharge during hypoxia hypercapnia determined expression of Liver Kinase B1 (LKB1), principal kinase activates AMP-activated protein (AMPK) metabolic stresses. Conversely, conditional deletion in catecholaminergic cells AMPK had no effect on responses or hypercapnia. By contrast, HVR was attenuated LKB1 deletion....
Vascular smooth muscle cells (VSMCs) provide vital contractile force within blood vessel walls, yet can also propagate cardiovascular pathologies through proliferative and pro-inflammatory activities. Such phenotypes are driven, in part, by the diverse effects of long non-coding RNAs (lncRNAs) on gene expression. However, lncRNA characterisation VSMCs pathological states is hampered incomplete representation reference annotation. We aimed to improve such contexts assembling non-reference...
ABSTRACT We recently demonstrated that the role of AMP-activated protein kinase ( AMPK ), a ubiquitously expressed enzyme governs cell-autonomous metabolic homeostasis, has been extended to system-level control breathing and thus oxygen energy (ATP) supply body. Here we assess contribution hypoxic ventilatory response (HVR) two upstream kinases govern activities AMPK. Lkb1, which activates in stress CaMKK2 mediates alternative Ca 2+ -dependent mechanism activation. HVRs remained unaffected...
Abstract The hypoxic ventilatory response (HVR) is critical to breathing and thus oxygen supply the body primarily mediated by carotid bodies. Here we reveal that afferent discharge during hypoxia hypercapnia determined expression of Liver Kinase B1 (LKB1), principal kinase activates AMP-activated protein (AMPK) metabolic stresses. Conversely, conditional deletion in catecholaminergic cells AMPK had no effect on responses or hypercapnia. By contrast, HVR was attenuated LKB1 deletion....
Abstract The hypoxic ventilatory response (HVR) is critical to breathing and thus oxygen supply the body primarily mediated by carotid bodies. Here we reveal that afferent discharge during hypoxia hypercapnia determined expression of Liver Kinase B1 (LKB1), principal kinase mediates AMPK activation metabolic stresses. Conversely, conditional deletion in catecholaminergic cells AMPK, downstream target LKB1, had no effect on responses or hypercapnia. By contrast, HVR was attenuated LKB1...