M. Harold Laughlin
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View article: Glycolysis-enhancing α1-adrenergic antagonists are neuroprotective in Alzheimer’s disease
Glycolysis-enhancing α1-adrenergic antagonists are neuroprotective in Alzheimer’s disease Open
Terazosin (TZ) is an α 1 -adrenergic receptor antagonist that enhances glycolysis by activating the enzyme phosphoglycerate kinase 1 (PGK1). Epidemiological data suggest that TZ may be neuroprotective in Parkinson’s disease and in dementia…
View article: Functional and structural adaptations of the coronary macro- and microvasculature to regular aerobic exercise by activation of physiological, cellular, and molecular mechanisms: ESC Working Group on Coronary Pathophysiology and Microcirculation position paper
Functional and structural adaptations of the coronary macro- and microvasculature to regular aerobic exercise by activation of physiological, cellular, and molecular mechanisms: ESC Working Group on Coronary Pathophysiology and Microcirculation position paper Open
Regular aerobic exercise (RAEX) elicits several positive adaptations in all organs and tissues of the body, culminating in improved health and well-being. Indeed, in over half a century, many studies have shown the benefit of RAEX on cardi…
View article: Dystrophin deficiency impairs vascular structure and function in the canine model of <scp>Duchenne</scp> muscular dystrophy
Dystrophin deficiency impairs vascular structure and function in the canine model of <span>Duchenne</span> muscular dystrophy Open
Duchenne muscular dystrophy (DMD) is a muscle‐wasting disease caused by dystrophin deficiency. Vascular dysfunction has been suggested as an underlying pathogenic mechanism in DMD. However, this has not been thoroughly studied in a large a…
View article: eNOS deletion impairs mitochondrial quality control and exacerbates Western diet-induced NASH
eNOS deletion impairs mitochondrial quality control and exacerbates Western diet-induced NASH Open
Dysregulated mitochondrial quality control leads to mitochondrial functional impairments that are central to the development and progression of hepatic steatosis to nonalcoholic steatohepatitis (NASH). Here, we identify hepatocellular loca…
View article: Differential impact of severe familial hypercholesterolemia on regional skeletal muscle and organ blood flows during exercise: Effects of <scp>PDE</scp>5 inhibition
Differential impact of severe familial hypercholesterolemia on regional skeletal muscle and organ blood flows during exercise: Effects of <span>PDE</span>5 inhibition Open
Objective Swine with familial hypercholesterolemia ( FH ) exhibit attenuated exercise‐induced systemic vasodilation that is restored by phosphodiesterase 5 ( PDE 5) inhibition. Whether the impacts of FH and PDE 5 inhibition to impair and r…
View article: Chronic interval exercise training prevents BK<sub>Ca</sub> channel-mediated coronary vascular dysfunction in aortic-banded miniswine
Chronic interval exercise training prevents BK<sub>Ca</sub> channel-mediated coronary vascular dysfunction in aortic-banded miniswine Open
Conventional treatments have failed to improve the prognosis of heart failure with preserved ejection fraction (HFpEF) patients. Thus, the purpose of this study was to determine the therapeutic efficacy of chronic interval exercise trainin…
View article: Microvascular insulin resistance in skeletal muscle and brain occurs early in the development of juvenile obesity in pigs
Microvascular insulin resistance in skeletal muscle and brain occurs early in the development of juvenile obesity in pigs Open
Impaired microvascular insulin signaling may develop before overt indices of microvascular endothelial dysfunction and represent an early pathological feature of adolescent obesity. Using a translational porcine model of juvenile obesity, …
View article: A chronic physical activity treatment in obese rats normalizes the contributions of ET-1 and NO to insulin-mediated posterior cerebral artery vasodilation
A chronic physical activity treatment in obese rats normalizes the contributions of ET-1 and NO to insulin-mediated posterior cerebral artery vasodilation Open
This study tested the hypotheses that obesity-induced decrements in insulin-stimulated cerebrovascular vasodilation would be normalized with acute endothelin-1a receptor antagonism and that treatment with a physical activity intervention r…
View article: Vascular Adaptation to Exercise in Humans: Role of Hemodynamic Stimuli
Vascular Adaptation to Exercise in Humans: Role of Hemodynamic Stimuli Open
On the 400th anniversary of Harvey's Lumleian lectures, this review focuses on “hemodynamic” forces associated with the movement of blood through arteries in humans and the functional and structural adaptations that result from repeated ep…
View article: Transcriptomic effects of metformin in skeletal muscle arteries of obese insulin-resistant rats
Transcriptomic effects of metformin in skeletal muscle arteries of obese insulin-resistant rats Open
We examined the effects of metformin, a commonly used antidiabetic drug, on gene expression in multiple arteries. Specifically, transcriptional profiles of feed arteries and second branch order arterioles in the soleus, gastrocnemius, and …
View article: The protective role of sex hormones in females and exercise prehabilitation in males on sternotomy-induced cranial hypoperfusion in aortic banded mini-swine
The protective role of sex hormones in females and exercise prehabilitation in males on sternotomy-induced cranial hypoperfusion in aortic banded mini-swine Open
During cardiac surgery, specifically sternotomy, cranial hypoperfusion is linked to cerebral ischemia, increased risk of perioperative watershed stroke, and other neurocognitive complications. The purpose of this study was to retrospective…
View article: A return to ad libitum feeding following caloric restriction promotes hepatic steatosis in hyperphagic OLETF rats
A return to ad libitum feeding following caloric restriction promotes hepatic steatosis in hyperphagic OLETF rats Open
Hyperphagic Otsuka Long-Evans Tokushima fatty (OLETF) rats develop obesity, insulin resistance, and nonalcoholic fatty liver disease (NAFLD), but lifestyle modifications, such as caloric restriction (CR), can prevent these conditions. We s…
View article: Effects of acute and chronic interval sprint exercise performed on a manually propelled treadmill on upper limb vascular mechanics in healthy young men
Effects of acute and chronic interval sprint exercise performed on a manually propelled treadmill on upper limb vascular mechanics in healthy young men Open
Interval sprint exercise performed on a manually propelled treadmill, where the hands grip the handle bars, engages lower and upper limb skeletal muscle, but little is known regarding the effects of this exercise modality on the upper limb…
View article: Carotid Artery Vascular Mechanics Serve as Biomarkers of Cognitive Dysfunction in Aortic‐Banded Miniature Swine That Can Be Treated With an Exercise Intervention
Carotid Artery Vascular Mechanics Serve as Biomarkers of Cognitive Dysfunction in Aortic‐Banded Miniature Swine That Can Be Treated With an Exercise Intervention Open
Background Cognitive impairment in the setting of heart failure with preserved ejection fraction remains poorly understood. Using aortic‐banded miniature swine displaying pathological features of human heart failure with preserved ejection…
View article: Aerobic exercise training in the treatment of non‐alcoholic fatty liver disease related fibrosis
Aerobic exercise training in the treatment of non‐alcoholic fatty liver disease related fibrosis Open
Key points Physiologically relevant rodent models of non‐alcoholic steatohepatitis (NASH) that resemble the human condition are limited. Exercise training and energy restriction are first‐line recommendations for the treatment of NASH. Hyp…
View article: Physical activity-induced remodeling of vasculature in skeletal muscle: role in treatment of type 2 diabetes
Physical activity-induced remodeling of vasculature in skeletal muscle: role in treatment of type 2 diabetes Open
This manuscript summarizes and discusses adaptations of skeletal muscle vasculature induced by physical activity and applies this understanding to benefits of exercise in prevention and treatment of type 2 diabetes (T2D). Arteriolar trees …
View article: Impact of 2‐Weeks Continuous Increase in Retrograde Shear Stress on Brachial Artery Vasomotor Function in Young and Older Men
Impact of 2‐Weeks Continuous Increase in Retrograde Shear Stress on Brachial Artery Vasomotor Function in Young and Older Men Open
Background Although acute elevation in retrograde shear rate ( SR ) impairs endothelial function, no previous study has explored the effect of prolonged elevation of retrograde SR on conduit artery vascular function. We examined the effect…
View article: Exercise training causes differential changes in gene expression in diaphragm arteries and 2A arterioles of obese rats
Exercise training causes differential changes in gene expression in diaphragm arteries and 2A arterioles of obese rats Open
We employed next-generation, transcriptome-wide RNA sequencing (RNA-Seq) technology to assess the effects of two different exercise training protocols on transcriptional profiles in diaphragm second-order arterioles (D2a) and in the diaphr…
View article: Exercise-induced differential changes in gene expression among arterioles of skeletal muscles of obese rats
Exercise-induced differential changes in gene expression among arterioles of skeletal muscles of obese rats Open
Using next-generation, transcriptome-wide RNA sequencing (RNA-Seq) technology we assessed the effects of exercise training on transcriptional profiles in skeletal muscle arterioles isolated from the soleus and gastrocnemius muscles of Otsu…
View article: Divergent role of nitric oxide in insulin-stimulated aortic vasorelaxation between low- and high-intrinsic aerobic capacity rats
Divergent role of nitric oxide in insulin-stimulated aortic vasorelaxation between low- and high-intrinsic aerobic capacity rats Open
Low-intrinsic aerobic capacity is associated with increased risk for cardiovascular and metabolic diseases and is a strong predictor of early mortality. The effects of intrinsic aerobic capacity on the vascular response to insulin are larg…
View article: Impaired Coronary Endothelial Vasorelaxation in a Preclinical Model of Peripheral Arterial Insufficiency
Impaired Coronary Endothelial Vasorelaxation in a Preclinical Model of Peripheral Arterial Insufficiency Open
The present study was designed to determine whether adult swine with peripheral artery insufficiency (PAI) would exhibit vascular dysfunction in vessels distinct from the affected distal limbs, the coronary conduit arteries. Moreover, we s…
View article: Combining metformin therapy with caloric restriction for the management of type 2 diabetes and nonalcoholic fatty liver disease in obese rats
Combining metformin therapy with caloric restriction for the management of type 2 diabetes and nonalcoholic fatty liver disease in obese rats Open
Weight loss is recommended for patients with nonalcoholic fatty liver disease (NAFLD), while metformin may lower liver enzymes in type 2 diabetics. Yet, the efficacy of the combination of weight loss and metformin in the treatment of NAFLD…
View article: Modulation of endothelial cell phenotype by physical activity: impact on obesity-related endothelial dysfunction
Modulation of endothelial cell phenotype by physical activity: impact on obesity-related endothelial dysfunction Open
Increased levels of physical activity are associated with reduced cardiovascular disease (CVD) risk and mortality in obesity and diabetes. Available evidence suggests that local factors, including local hemodynamics, account for a signific…
View article: Chronic NOS inhibition accelerates NAFLD progression in an obese rat model
Chronic NOS inhibition accelerates NAFLD progression in an obese rat model Open
The progression in nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis is a serious health concern, but the underlying mechanisms remain unclear. We hypothesized that chronic inhibition of nitric oxide (NO) synthase (N…