Helen Elizabeth CollinsUniversity of Louisville | UL · School of Medicine
Helen Elizabeth Collins
BSc (Hons), PhD
About
42
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Introduction
I run an R01 funded laboratory focused on understanding the mechanisms contributing to female cardiovascular health and resilience.
Additional affiliations
Education
October 2006 - December 2010
October 2003 - July 2006
Publications
Publications (42)
Introduction: The general population is becoming more obese, and diabetes rates continue to rise, with overnutrition and consumption of processed foods likely contributing factors. Many people consume diets high in fat, sugar, and salt; however, this triad of factors is rarely examined in unison in studies. In addition, studies that examined diets...
Research utilizing animals depends on the generation of offspring for use in experiments or for the maintenance of animal colonies. While not considered by all, several different factors preceding and during pregnancy, as well as during lactation, can program various characteristics in the offspring. Here, we present the most common models of devel...
Maternal mortality rates are at an all-time high across the world and are set to increase in subsequent years. Cardiovascular disease is the leading cause of death during pregnancy and postpartum, especially in the US. Therefore, understanding the physiological changes in the cardiovascular system during normal pregnancy is necessary to understand...
Myocardial perfusion is inextricably coupled to metabolism, with increases in physiologic cardiac demand promoting coronary vasodilation. Despite its wide acceptance, the hypothesis that cardiomyocyte metabolism autoregulates myocardial perfusion lacks mechanistic detail; however, clinical and preclinical studies suggest a signaling role for interm...
The goal of the present study was to characterize changes in mitochondrial respiration in the maternal heart during pregnancy and after birth. Timed pregnancy studies were performed in 12-week-old female FVB/NJ mice, and cardiac mitochondria were isolated from the following groups of mice: non-pregnant (NP), mid-pregnancy (MP), late-pregnancy (LP),...
Mitochondria morphology and function, and their quality control by mitophagy, are essential for heart function. We investigated whether these are influenced by time of the day (TOD), sex, and fed or fasting status, using transmission electron microscopy (EM), mitochondrial electron transport chain (ETC) activity, and mito-QC reporter mice. We obser...
Purpose of Review
Pregnancy and exercise are systemic stressors that promote physiological growth of the heart in response to repetitive volume overload and maintenance of cardiac output. This type of remodeling is distinct from pathological hypertrophy and involves different metabolic mechanisms that facilitate growth; however, it remains unclear...
During pregnancy, the maternal heart undergoes physiological cardiac growth, reversing following parturition; however, the contributing underlying processes are largely unknown. Changes in cardiac metabolism appear to be associated with cardiac growth through a reduction in glucose catabolism. We have also shown that several cardiac metabolic trans...
Autophagy is important for protein and organelle quality control. Growing evidence demonstrates that autophagy is tightly controlled by transcriptional mechanisms, including repression by zinc finger containing KRAB and SCAN domains 3 (ZKSCAN3). We hypothesize that cardiomyocyte-specific ZKSCAN3 knockout (Z3K) disrupts autophagy activation and repr...
For years, females were thought of as smaller men with complex hormonal cycles; as a result, females have been largely excluded from preclinical and clinical research. However, in the last ten years, with the increased focus on sex as a biological variable, it has become clear that this is not the case, and in fact, male and female cardiovascular b...
Introduction: During pregnancy, the maternal heart undergoes physiological cardiac growth, which reverses following parturition; however, the underlying processes that contribute are largely unknown. Changes in both systemic and cardiac metabolism appear to be associated with cardiac growth, which could also contribute during pregnancy. We have sho...
During pregnancy, the maternal heart undergoes physiologic growth, which reverses following parturition and is associated with the restoration of hemodynamic parameters. However, the molecular processes underlying the reversal of pregnancy-induced cardiac growth and the time frame in which these changes occur remain unclear. Because changes in card...
Although the structural and functional effects of exercise on the heart are well established, the metabolic changes that occur in the heart during and after exercise remain unclear. In this study, we used metabolomics to assess time-dependent changes in the murine cardiac metabolome following 1 session of treadmill exercise. After the exercise bout...
The goal of this study was to develop an atlas of the metabolic, transcriptional, and proteomic changes that occur with pregnancy in the maternal heart. Timed pregnancy studies in FVB/NJ mice revealed significant increases in heart size by day 8 of pregnancy (mid-pregnancy; MP), which was sustained throughout the rest of the term compared with non-...
Tight spatiotemporal regulation of intracellular Ca2+ plays a critical role in regulating diverse cellular functions including cell survival, metabolism, and transcription. As a result, eukaryotic cells have developed a wide variety of mechanisms for controlling Ca2+ influx and efflux across the plasma membrane as well as Ca2+ release and uptake fr...
Stromal interaction molecule 1 (STIM1) is a major regulator of store-operated calcium entry in non-excitable cells. Recent studies have suggested that STIM1 plays a role in pathological hypertrophy; however, the physiological role of STIM1 in the heart is not well understood. We have shown that mice with a cardiomyocyte deletion of STIM1 (cr STIM1-...
The modification of proteins by O-linked β- N -acetylglucosamine (O-GlcNAc) is associated with the regulation of numerous cellular processes. Despite the importance of O-GlcNAc in mediating cellular function our understanding of the mechanisms that regulate O-GlcNAc levels is limited. One factor known to regulate protein O-GlcNAc levels is nutrient...
During pregnancy, the maternal heart undergoes reversible, physiologic growth, which supports cardiac output and maintains the physiologic demands of the growing fetus and mother; however, the molecular processes underlying pregnancy-induced cardiac growth are unclear. It is well known that changes in metabolism influence cardiac remodeling, and re...
Introduction: Previous studies report that many systemic adaptations occur early in an exercise training program, but how exercise leads to cardiac adaptations remain unclear. In this study, we characterized time-dependent changes in cardiac metabolism and gene expression following an acute session of aerobic exercise.
Methods: We used untargeted m...
Transmission electron microscopy (TEM) has long been an important technique, capable of high degree resolution and visualization of subcellular structures and organization. Over the last 20 years, TEM has gained popularity in the cardiovascular field to visualize changes at the nanometer scale in cardiac ultrastructure during cardiovascular develop...
Cardiovascular disease is the leading cause of death in pregnant and postpartum women. During pregnancy, the maternal heart rapidly adapts to the increasing physiological and metabolic demands of the growing fetus. This adaptation often takes the form of a physiological hypertrophy in which the maternal heart grows to increase cardiac output; howev...
The post-translational modification of serine and threonine residues of nuclear, cytosolic, and mitochondrial proteins by O-linked β-N-acetyl glucosamine (O-GlcNAc) has long been seen as an important regulatory mechanism in the cardiovascular system. O-GlcNAcylation of cardiac proteins has been shown to contribute to the regulation of transcription...
The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function. Importantly, the O-GlcNAc modification of mitochondrial proteins has been identified as a potential mechanism to modulate me...
The endoplasmic reticulum/sarcoplasmic reticulum Ca2+ sensor stromal interaction molecule 1 (STIM1), a key mediator of store-operated Ca2+ entry, is expressed in cardiomyocytes and has been implicated in regulating multiple cardiac processes, including hypertrophic signaling. Interestingly, cardiomyocyte-restricted deletion of STIM1 (crSTIM1-KO) re...
Recent studies suggest that the time of day at which food is consumed dramatically influences clinically-relevant cardiometabolic parameters (e.g., adiposity, insulin sensitivity, and cardiac function). Meal feeding benefits may be the result of daily periods of feeding and/or fasting, highlighting the need for improved understanding of the tempora...
The post-translational modification of serine and threonine residues of proteins found in numerous subcellular locations by O-linked N-acetylglucosamine (O-GlcNAc) is emerging as a key mediator of many cardiovascular pathophysiological processes. Early studies implicated increased protein O-GlcNAcylation as contributing to the cardiovascular compli...
The ER/SR Ca ²⁺ sensor, Stromal Interaction molecule 1 (STIM1), a key regulator of store-operated calcium entry is expressed in cardiomyocytes and has been implicated in regulating hypertrophic signaling. We have recently shown that mice with a cardiomyocyte-restricted deletion of STIM1 develop dilated cardiomyopathy. Given the importance of Ca ²⁺...
Our understanding of the role of protein O-GlcNAcylation in the regulation of the cardiovascular system has increased rapidly in recent years. Studies have linked increased
O-GlcNAc levels to glucose toxicity and diabetic complications; conversely, acute activation of O-GlcNAcylation has been shown to be cardioprotective. However, it is also increa...
This editorial refers to ‘Emergence of Orai3 activity during cardiac hypertrophy’ by Y. Saliba et al. , doi:10.1093/cvr/cvu207 .
Our understanding of cardiomyocyte Ca2+ handling is primarily based on the regulation of voltage-gated Ca2+ entry, via L-type Ca2+ channels (LTCCs), and the resulting Ca2+-induced Ca2+ release from the sarcoplasmic retic...
Circadian clocks are cell autonomous, transcriptionally based, molecular mechanisms that confer the selective advantage of anticipation, enabling cells/organs to respond to environmental factors in a temporally appropriate manner. Critical to circadian clock function are 2 transcription factors, CLOCK and BMAL1. The purpose of the present study was...
Store‐operated Ca ²⁺ entry (SOCE) and its molecular mediator, the endoplasmic reticulum (ER) Ca ²⁺ sensor, Stromal interaction molecule 1 (STIM1) have been implicated in hypertrophic signaling. However, since the physiological role of STIM1 in the adult heart remains unknown, we developed a cardiomyocyte‐restricted STIM1 knockout ( cr STIM1‐KO) mou...
The endoplasmic reticulum (ER) Ca(2+) sensor, stromal interaction molecule 1 (STIM1), has been implicated as a key mediator of store-dependent and store-independent Ca(2+) entry (SOCE) pathways, and maintenance of ER structure. STIM1 is present in embryonic, neonatal and adult cardiomyocytes and has been strongly implicated in hypertrophic signalin...
Store-operated Ca(2+) entry (SOCE) is critical for Ca(2+) signaling in non-excitable cells; however, its role in the regulation of cardiomyocyte Ca(2+) homeostasis has only recently been investigated. The increased understanding of the role of Stromal Interaction Molecule 1 (STIM1) in regulating SOCE combined with recent studies demonstrating the p...
: Excitation-contraction coupling of the normotensive rat heart exhibits a time-of-day variation in its response to isoproterenol (ISO), with a decrease during the animal's active period. Pressure-induced hypertrophy is known to adversely affect the circadian clock in the heart and this study sets out to determine whether this alters the time-of-da...
The innervation of the mouse internal anal sphincter (IAS) has been little studied, and how it changes during aging has not previously been investigated. The aim of this study was therefore to characterize the distribution and density of subtypes of nerve fibers in the IAS and underlying mucosa in 3-, 12- to 13-, 18- and 24- to 25-month-old male C5...
Although >10% of cardiac gene expression displays diurnal variations, little is known of their impact on excitation-contraction coupling.
To determine whether the time of day affects excitation-contraction coupling in rat ventricles.
Left ventricular myocytes were isolated from rat hearts at 2 opposing time points, corresponding to the animals rest...