Rebecca H Ritchie

Rebecca H Ritchie
Baker Heart and Diabetes Institute · Heart Failure Pharmacology Research Group

B.Sc(Hons) PhD

About

228
Publications
18,544
Reads
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5,960
Citations
Citations since 2016
94 Research Items
3764 Citations
20162017201820192020202120220200400600
20162017201820192020202120220200400600
20162017201820192020202120220200400600
20162017201820192020202120220200400600
Additional affiliations
December 2002 - present
Baker Heart and Diabetes Institute
Position
  • Laboratory Head
July 1997 - November 2002
January 1995 - June 1997
Wayne State University
Position
  • Fellow

Publications

Publications (228)
Article
Full-text available
Cardiovascular disease (CVD) remains the leading cause of death worldwide. An ongoing challenge remains the development of novel pharmacotherapies to treat CVD, particularly atherosclerosis. Effective mechanism-informed development and translation of new drugs requires a deep understanding of the known and currently unknown biological mechanisms un...
Article
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MicroRNA 34a (miR-34a) is elevated in the heart in a setting of cardiac stress or pathology, and we previously reported that inhibition of miR-34a in vivo provided protection in a setting of pressure overload-induced pathological cardiac hypertrophy and dilated cardiomyopathy. Prior work had also shown that circulating or cardiac miR-34a was elevat...
Article
Lower extremity artery disease (LEAD) is a chronic inflammatory disease that occurs when atherosclerotic plaques form in the lower extremities, which may lead to amputation if not manged properly. Given clinical standardcare (pharmacological and surgical) have limited efficacy in LEAD, developing novel strategies to manage LEAD remains an unmet cli...
Article
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We discuss the fascinating pharmacology of formylpeptide receptor‐2 (FPR2; often referred to as FPR2/ALX since it binds lipoxin A4). Initially identified as a low‐affinity ‘relative’ of FPR1, FPR2 presents complex and diverse biology. For instance, it is activated by several classes of agonists (from peptides to proteins and lipid mediators) and di...
Article
Patients with diabetes have an increased risk of developing heart failure, preceded by (often asymptomatic) cardiac abnormalities, collectively called diabetic cardiomyopathy (DC). Diabetic heart failure lacks effective treatment, remaining an urgent, unmet clinical need. Although structural and functional characteristics of the diabetic human hear...
Article
Full-text available
Patients with Type 2 diabetes mellitus (T2DM) frequently exhibit a distinctive cardiac phenotype known as diabetic cardiomyopathy. Cardiac complications associated with T2DM include cardiac inflammation, hypertrophy, fibrosis and diastolic dysfunction in the early stages of the disease, which can progress to systolic dysfunction and heart failure....
Article
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Background and purpose: The risk of fatal cardiovascular events is increased in patients with type 2 diabetes mellitus (T2DM). A major contributor to poor prognosis is impaired nitric oxide (NO•) signalling at the level of tissue responsiveness, termed NO• resistance. This study aimed to determine if T2DM promotes NO• resistance in the heart and v...
Article
A significant cardiac complication of diabetes is cardiomyopathy, a form of ventricular dysfunction that develops independently of coronary artery disease, hypertension and valvular diseases, which may subsequently lead to heart failure. Several structural features underlie the development of diabetic cardiomyopathy and eventual diabetes‐induced he...
Article
Diabetes is associated with an increased risk of heart failure (HF). This is commonly termed diabetic cardiomyopathy and is often characterised by increased cardiac fibrosis, pathological hypertrophy, increased oxidative and endoplasmic reticulum stress as well as diastolic dysfunction. Adiponectin is a cardioprotective adipokine that is downregula...
Article
Full-text available
Diabetes is a major contributor to the increasing burden of heart failure prevalence globally, at least in part due to a disease process termed diabetic cardiomyopathy. Diabetic cardiomyopathy is characterised by cardiac structural changes that are caused by chronic exposure to the diabetic milieu. These structural changes are a major cause of left...
Article
Introduction: The risk of fatal cardiovascular events is increased in patients with type 2 diabetes mellitus (T2DM). A major contributor to poor prognosis is impaired nitric oxide (NO•) signalling at the level of tissue responsiveness, termed NO• resistance. Nitroxyl (HNO) induces positive inotropic and lusitropic effects in healthy and failing hea...
Article
Introduction: We have previously demonstrated that the naturally-occurring anti-inflammatory and pro-resolving protein Annexin-A1 (Anx-A1) limits the acute inflammatory response post myocardial infarction, but its impact on chronic inflammation, such as hypertension, has not been explored. This study aims to investigate the role of Anx-A1 in a prec...
Article
Background: Diabetes is associated with a significantly elevated risk of heart failure. However, the precise cellular and molecular protagonists underpinning the development of heart failure in diabetes remains unclear. Moreover, very little is known, of how disparate non-myocyte populations of the heart contribute to diabetic cardiomyopathy. Metho...
Article
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People affected by diabetes are at an increased risk of developing heart failure than their non-diabetic counterparts, attributed in part to a distinct cardiac pathology termed diabetic cardiomyopathy. Mitochondrial dysfunction and excess reactive oxygen species (ROS) have been implicated in a range of diabetic complications and are a common featur...
Article
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Long-term nicotine intake is associated with an increased risk of myocardial damage and dysfunction. However, it remains unclear whether targeting mitochondrial reactive oxygen species (ROS) prevents nicotine-induced cardiac remodeling and dysfunction. This study investigated the effects of mitoTEMPO (a mitochondria-targeted antioxidant), and resve...
Preprint
Full-text available
Diabetic heart disease is highly prevalent and characterized by diastolic dysfunction. The mechanisms of diabetic heart disease are poorly understood and no targeted therapies are available. Here we show that the diabetic myocardium (type 1 and type 2) is characterized by marked glycogen elevation and ectopic cellular localization - a paradoxical m...
Article
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Diabetes increases the prevalence of heart failure by 6–8-fold, independent of other comorbidities such as hypertension and coronary artery disease, a phenomenon termed diabetic cardiomyopathy. Several key signalling pathways have been identified that drive the pathological changes associated with diabetes-induced heart failure. This has led to the...
Article
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Background Diabetes is associated with a significantly elevated risk of cardiovascular disease and its specific pathophysiology remains unclear. Recent studies have changed our understanding of cardiac cellularity, with cellular changes accompanying diabetes yet to be examined in detail. This study aims to characterise the changes in the cardiac ce...
Article
Aims: The glucose-driven enzymatic modification of myocardial proteins by the sugar moiety, β-N-acetylglucosamine (O-GlcNAc), is increased in pre-clinical models of diabetes, implicating protein O-GlcNAc modification in diabetes-induced heart failure. Our aim was to specifically examine cardiac manipulation of the two regulatory enzymes of this pr...
Article
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Conclusion Both NO• and HNO contribute to endothelium-dependent relaxation in carotid arteries. In diabetes, NO•-mediated relaxation is impaired, whereas HNO-mediated relaxation was preserved. The potential for preserved HNO activity under pathological conditions that are associated with oxidative stress indicates that HNO donors may represent a vi...
Article
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Non-alcoholic steatohepatitis (NASH) develops from non-alcoholic fatty liver disease (NAFLD). Currently, around 25% of the population is estimated to have NAFLD, and 25% of NAFLD patients are estimated to have NASH. NASH is typically characterized by liver steatosis inflammation, and fibrosis driven by metabolic disruptions such as obesity, diabete...
Article
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Purpose: HFpEF (heart failure with preserved ejection fraction) is a major consequence of diabetic cardiomyopathy with no effective treatments. Here, we have characterized Akita mice as a preclinical model of HFpEF and used it to confirm the therapeutic efficacy of the mitochondria-targeted dicarbonyl scavenger, MitoGamide. Methods and results:...
Article
Background: Inflammation can play an important role in the progression of hypertension and end organ damage, yet anti-inflammatory drugs remain relatively underexplored as antihypertensive therapeutic options. Formyl peptide receptors (FPR) are integral to the regulation and resolution of inflammation and may be an attractive target for the treatme...
Chapter
Open image in new window Both nitric oxide (NO) and nitroxyl (HNO) donors signal through soluble guanylyl cyclase (sGC). NO binds to the Fe(II) form of sGC and nitroxyl possibly to both sGC heme and thiol groups. In the vasculature, nitroxyl can also signal through voltage-dependent (Kv) and ATP-sensitive (KATP) K⁺ channels as well as calcitonin ge...
Article
Introduction: It is estimated that 15-30% of hypertensive patients are resistant to available drugs; and thus identifying novel therapeutic strategies is imperative. We have previously demonstrated that the formyl peptide receptor-1/2 (FPR) small-molecule agonist, Cmpd17b, exhibits anti-inflammatory and vasodilator actions. We investigated the effi...
Article
Diabetes mellitus predisposes affected individuals to a significant spectrum of cardiovascular complications, one of the most debilitating in terms of prognosis is heart failure. Indeed, the increasing global prevalence of diabetes mellitus and an aging population has given rise to an epidemic of diabetes mellitus-induced heart failure. Despite the...
Article
Full-text available
Diabetes is associated with an increased mortality risk due to cardiovascular complications. Hyperglycemia-induced oxidative stress underlies these complications, leading to an impairment in endogenous nitric oxide (NO•) generation, together with reductions in NO• bioavailability and NO• responsiveness in the vasculature, platelets and myocardium....
Article
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The article "The Mitochondria-Targeted Methylglyoxal Sequestering Compound, MitoGamide, Is Cardioprotective in the Diabetic Heart".
Article
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The incidence of diabetes and its association with increased cardiovascular disease risk represents a major health issue worldwide. Diabetes-induced hyperglycemia is implicated as a central driver of responses in the diabetic heart such as cardiomyocyte hypertrophy, fibrosis, and oxidative stress, termed diabetic cardiomyopathy. The onset of these...
Article
Full-text available
The formyl peptide receptor (FPR) family are a group of G-protein coupled receptors that play an important role in the regulation of inflammatory processes. It is well-established that activation of FPRs can have cardioprotective properties. Recently, more stable small-molecule FPR1/2 agonists have been described, including both Compound 17b (Cmpd1...
Article
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Several studies have shown that failure to resolve inflammation may contribute to the progression to many chronic inflammatory disorders. It is thus essential to balance the initial phase and resolution phase of inflammation. It has been suggested that targeting resolution of inflammation might be a novel therapeutic approach for chronic inflammato...
Article
Increased exposure to nicotine contributes to the development of cardiac dysfunction by promoting oxidative stress, fibrosis, and inflammation. These deleterious events altogether render cardiac myocytes more susceptible to acute cardiac insults such as ischemia-reperfusion (I/R) injury. This study sought to elucidate the role of angiotensin II typ...
Article
Background and purpose: Arterial stiffness, a hallmark of diabetes, increases the risk of cardiovascular complications. Potential mechanisms that promote arterial stiffness in diabetes include oxidative stress, glycation and inflammation. The anti-inflammatory protein annexin-A1 (AnxA1) has cardioprotective properties, particularly in the context...
Article
Full-text available
The increasing burden of heart failure globally can be partly attributed to the increased prevalence of diabetes, and the subsequent development of a distinct form of heart failure known as diabetic cardiomyopathy. Despite this, effective treatment options have remained elusive, due partly to the lack of an experimental model that adequately mimics...
Article
Full-text available
Purpose Methylglyoxal, a by-product of glycolysis and a precursor in the formation of advanced glycation end-products, is significantly elevated in the diabetic myocardium. Therefore, we sought to investigate the mitochondria-targeted methylglyoxal scavenger, MitoGamide, in an experimental model of spontaneous diabetic cardiomyopathy. Methods Male...
Article
Background and purpose: Endothelium-derived vasoconstriction is a hallmark of vascular dysfunction in hypertension. In some cases, an overproduction of endothelium-derived prostacyclin (PGI2 ) can cause contraction rather than relaxation. Relaxin is well known for its vasoprotective actions, but the possibility that this peptide could also reverse...
Article
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Background: Ischemia reperfusion injury (I/RI) is a common complication of cardiovascular diseases. Resolution of detrimental I/RI-generated pro-thrombotic and pro-inflammatory responses is essential to restore homeostasis. Platelets play a crucial part in the integration of thrombosis and inflammation. Their role as participants in the resolution...
Article
Herein we describe the development of a focused series of functionalized pyridazin-3(2H)-one-based formyl peptide receptors (FPR) agonists which demonstrate high potency and biased agonism. The compounds described demonstrated biased activation of pro-survival signaling - ERK1/2 phosphorylation – through diminution of the detrimental FPR1/2-mediate...
Article
Full-text available
The anti-inflammatory, pro-resolving annexin-A1 protein acts as an endogenous brake against exaggerated cardiac necrosis, inflammation, and fibrosis following myocardial infarction (MI) in vivo. Little is known, however, regarding the cardioprotective actions of the N-terminal-derived peptide of annexin A1, Ac2-26, particularly beyond its anti-necr...
Article
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Background High-fat feeding and hyperglycemia, key risk factors for the development of metabolic syndrome (MetS), are emerging to associate with increased risk of developing dementia and cognitive decline. Despite this, clinical and experimental studies have yet to elucidate the specific contributions of either high-fat feeding or hyperglycemia to...
Article
Background Type 2 diabetes and associated vascular complications cause substantial morbidity and mortality. It is important to investigate mechanisms and test therapies in relevant physiological models, yet few animal models adequately recapitulate all aspects of the human condition. Objective: We sought to determine the potential of using an insul...
Article
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Heart failure (HF) is a debilitating and deadly chronic disease, with almost 50% of patients with HF dying within 5 years of diagnosis. With limited effective therapies to treat or cure HF, new therapies are greatly needed. microRNAs (miRNAs) are small non-coding RNA molecules that are powerful regulators of gene expression and play a key role in a...
Article
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A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Article
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Cardiovascular complications are the major cause of mortality in patients with diabetes. This is closely associated with both macrovascular and microvascular complications of diabetes, which lead to organ injuries in diabetic patients. Previous studies have consistently demonstrated the beneficial effects of relaxin treatment for protection of the...
Article
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It is now increasingly appreciated that inflammation is not limited to the control of pathogens by the host, but rather that sterile inflammation which occurs in the absence of viral or bacterial pathogens, accompanies numerous disease states, none more so than the complications that arise as a result of hyperglycaemia. Individuals with type 1 or t...
Article
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Diabetic cardiomyopathy is a distinct pathology characterized by early emergence of diastolic dysfunction. Increased cardiovascular risk associated with diabetes is more marked for women, but an understanding of the role of diastolic dysfunction in female susceptibility to diabetic cardiomyopathy is lacking. To investigate the sex-specific relation...
Article
Heart failure is a complex clinical syndrome, the incidence and prevalence of which is increased in diabetes mellitus, pre-diabetes, and obesity. Although this may arise from underlying coronary artery disease, it often occurs in the absence of significant major epicardial coronary disease, and most commonly manifests as heart failure with preserve...