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Journal of the American College of... Nov 2018
Topics: Denervation; Heart Failure; Humans; Kidney; Renin-Angiotensin System; Ventricular Remodeling
PubMed: 30466520
DOI: 10.1016/j.jacc.2018.09.027 -
Medicine Nov 2015Type 2 diabetes mellitus (T2DM) is a group of metabolic diseases of multiple etiologies. Although great progress has been made, researchers are still working on the... (Meta-Analysis)
Meta-Analysis Review
Type 2 diabetes mellitus (T2DM) is a group of metabolic diseases of multiple etiologies. Although great progress has been made, researchers are still working on the pathogenesis of T2DM and how to best use the treatments available. Aside from several novel pharmacological approaches, catheter-based sympathetic renal denervation (RDN) has gained a significant role in resistant hypertension, as well as improvements in glycemic control in T2DM.In this article, we will summarize herein the role sympathetic activation plays in the progression of T2DM and review the recent clinical RDN experience in glucose metabolism.We performed systematic review in online databases, including PubMed, EmBase, and Web of Science, from inception until 2015.Studies were included if a statistical relationship was investigated between RDN and T2DM.The quality of each included study was assessed by Newcastle-Ottawa scale score. To synthesize these studies, a random-effects model or a fixed-effects model was applied as appropriate. Then, we calculated heterogeneity, performed sensitivity analysis, tested publication bias, and did meta-regression analysis. Finally, we identified 4 eligible articles.In most studies, RDN achieved via novel catheter-based approach using radiofrequency energy has gained a significant role in resistant hypertension, as well as improvements in glycemic control in T2DM. But the DREAMS-Study showed that RDN did not change median insulin sensitivity nor systemic sympathetic activity.Firstly, the current published studies lacked a proper control group, along with the sample capacity was small. Also, data obtained in the subgroups of diabetic patients were not separately analyzed and the follow-up period was very short. In addition, a reduction in blood pressure accounts for the improvements in glucose metabolism and insulin resistance cannot be excluded.If the favorable result of better glucose metabolism is confirmed in large-scale, randomized studies, RDN may emerge as a novel therapeutic option for patients with T2DM.
Topics: Diabetes Mellitus, Type 2; Humans; Kidney; Sympathectomy
PubMed: 26554798
DOI: 10.1097/MD.0000000000001932 -
JACC. Cardiovascular Interventions Dec 2015
Topics: Catheter Ablation; Denervation; Humans; Hypertension; Hypertension, Pulmonary; Kidney; Pulmonary Artery; Renal Artery; Sympathectomy; Sympathetic Nervous System
PubMed: 26738674
DOI: 10.1016/j.jcin.2015.10.022 -
JACC. Cardiovascular Interventions Feb 2019
Topics: Denervation; Heart Failure; Humans; Hypertension, Pulmonary; Pulmonary Artery; Treatment Outcome
PubMed: 30732733
DOI: 10.1016/j.jcin.2018.10.045 -
American Journal of Nephrology 2024
Topics: Humans; Kidney; Sympathectomy; Hypertension; Animals
PubMed: 37651991
DOI: 10.1159/000533885 -
The Journal of Physiology Dec 2016Mitochondria are frequently implicated in the ageing of skeletal muscle, although the role of denervation in modulating mitochondrial function in ageing muscle is...
KEY POINTS
Mitochondria are frequently implicated in the ageing of skeletal muscle, although the role of denervation in modulating mitochondrial function in ageing muscle is unknown. We show that increased sensitivity to apoptosis initiation occurs prior to evidence of persistent denervation and is thus a primary mitochondrial defect in ageing muscle worthy of therapeutic targeting. However, at more advanced age, mitochondrial function changes are markedly impacted by persistent sporadic myofibre denervation, suggesting the mitochondrion may be a less viable therapeutic target.
ABSTRACT
Experimental denervation modulates mitochondrial function, where changes in both reactive oxygen species (ROS) and sensitivity to permeability transition are implicated in the resultant muscle atrophy. Notably, although denervation occurs sporadically in ageing muscle, its impact on ageing muscle mitochondria is unknown. Because this information has important therapeutic implications concerning targeting the mitochondrion in ageing muscle, we examined mitochondrial function in skeletal muscle from four groups of humans, comprising two active (mean ± SD age: 23.7 ± 2.7 years and 71.2 ± 4.9 years) and two inactive groups (64.8 ± 3.1 years and 82.5 ± 4.8 years), and compared this with a murine model of sporadic denervation. We tested the hypothesis that, although some alterations of mitochondrial function in aged muscle are attributable to a primary organelle defect, mitochondrial dysfunction would be impacted by persistent denervation in advanced age. Both ageing in humans and sporadic denervation in mice increased mitochondrial sensitivity to permeability transition (humans, P = 0.004; mice, P = 0.01). To determine the contribution of sporadic denervation to mitochondrial function, we pharmacologically inhibited the denervation-induced ROS response. This reduced ROS emission by 60% (P = 0.02) in sporadically denervated mouse muscle, which is similar to that seen in humans older than 75 years (-66%, P = 0.02) but not those younger than 75 years. We conclude that an increased sensitivity to permeability transition is a primary mitochondrial defect in ageing muscle. However, at more advanced age, when muscle atrophy becomes more clinically severe, mitochondrial function changes are markedly impacted by persistent sporadic denervation, making the mitochondrion a less viable therapeutic target.
Topics: Adult; Aged; Aged, 80 and over; Animals; Humans; Male; Mice, Transgenic; Middle Aged; Mitochondria, Muscle; Muscle Denervation; Muscle, Skeletal; Reactive Oxygen Species; Young Adult
PubMed: 27619626
DOI: 10.1113/JP272487 -
Archives of Cardiovascular Diseases 2014
Topics: Antihypertensive Agents; Blood Pressure; Drug Resistance; Evidence-Based Medicine; Humans; Hypertension; Kidney; Patient Selection; Randomized Controlled Trials as Topic; Risk Factors; Sympathectomy; Treatment Outcome
PubMed: 25128935
DOI: 10.1016/j.acvd.2014.06.006 -
JCI Insight Jul 2021Neurogenic muscle atrophy is the loss of skeletal muscle mass and function that occurs with nerve injury and in denervating diseases, such as amyotrophic lateral...
Neurogenic muscle atrophy is the loss of skeletal muscle mass and function that occurs with nerve injury and in denervating diseases, such as amyotrophic lateral sclerosis. Aside from prompt restoration of innervation and exercise where feasible, there are currently no effective strategies for maintaining skeletal muscle mass in the setting of denervation. We conducted a longitudinal analysis of gene expression changes occurring in atrophying skeletal muscle and identified growth arrest and DNA damage-inducible A (Gadd45a) as a gene that shows one of the earliest and most sustained increases in expression in skeletal muscle after denervation. We evaluated the role of this induction using genetic mouse models and found that mice lacking GADD45A showed accelerated and exacerbated neurogenic muscle atrophy, as well as loss of fiber type identity. Our genetic analyses demonstrate that, rather than directly contributing to muscle atrophy as proposed in earlier studies, GADD45A induction likely represents a protective negative feedback response to denervation. Establishing the downstream effectors that mediate this protective effect and the pathways they participate in may yield new opportunities to modify the course of muscle atrophy.
Topics: Amyotrophic Lateral Sclerosis; Animals; Atrophy; Cell Cycle Proteins; Disease Models, Animal; Feedback, Physiological; Gene Expression Profiling; Gene Expression Regulation; Mice; Muscle Denervation; Muscle, Skeletal; Muscular Atrophy; Protective Factors; Signal Transduction
PubMed: 34128833
DOI: 10.1172/jci.insight.149381 -
Journal of Pediatric Surgery Dec 2014Hirschsprung's disease is characterized by colonic aganglionosis, curable only by surgical correction. Stem cells may offer regenerative benefits while preventing...
INTRODUCTION
Hirschsprung's disease is characterized by colonic aganglionosis, curable only by surgical correction. Stem cells may offer regenerative benefits while preventing surgical risks. Existing Hirschsprung's model systems are limited by alimentary compromise and spontaneous ganglionic reconstitution. We endeavored to generate a model of permanent colonic aganglionosis to support longitudinal cell therapy studies.
METHODS
Among adult female Lewis rats (n=11), laparotomy was performed and one-centimeter segments of descending colon were isolated from continuity and denervated by trans-serosal benzalkonium chloride (BAC) exposure. Postoperative weights were plotted. The colon segments were retrieved after 50 or 100days. Immunohistochemical staining (IHC) for beta-III tubulin (TUJ1) and glial fibrillary acid protein (GFAP) revealed colonic ganglia. Muscle layer diameter and the presence of ganglia were contrasted between normal and denervated segments.
RESULTS
All animals survived, experienced 5% weight loss after one week, and then consistently gained weight. Isolated segments had significantly hypertrophied smooth muscle layers compared to normal colon. Ganglia were identified by IHC in normal colonic segments, and denervated colonic segments had no IHC evidence of myenteric ganglia.
CONCLUSION
Colonic segmental isolation and denervation result in an effective model of irreversible colonic aganglionosis. Animals retain alimentary function. Muscularis hypertrophy, myenteric denervation, and normal animal longevity are suitable for long-term studies of cell therapy.
Topics: Animals; Colon; Denervation; Disease Models, Animal; Female; Ganglia; Hirschsprung Disease; Rats; Rats, Inbred Lew
PubMed: 25487488
DOI: 10.1016/j.jpedsurg.2014.09.024 -
High Blood Pressure & Cardiovascular... Jan 2024In patients with end-stage renal disease (ESRD) undergoing haemodialysis, hypertension is of common detection and frequently inadequately controlled. Multiple... (Review)
Review
In patients with end-stage renal disease (ESRD) undergoing haemodialysis, hypertension is of common detection and frequently inadequately controlled. Multiple pathophysiological mechanisms are involved in the development and progression of the ESRD-related high blood pressure state, which has been implicated in the increased cardiovascular risk reported in this hypertensive clinical phenotype. Renal sympathetic efferent and afferent nerves play a relevant role in the development and progression of elevated blood pressure values in patients with ESRD, often leading to resistant hypertension. Catheter-based bilateral renal nerves ablation has been shown to exert blood pressure lowering effects in resistant hypertensive patients with normal kidney function. Promising data on the procedure in ESRD patients with resistant hypertension have been reported in small scale pilot studies. Denervation of the native non-functioning kidney's neural excitatory influences on central sympathetic drive could reduce the elevated cardiovascular morbidity and mortality seen in ESRD patients. The present review article will focus on the promising results obtained with renal denervation in patients with ESRD, its mechanisms of action and future perspectives in these high risk patients.
Topics: Humans; Sympathetic Nervous System; Sympathectomy; Kidney; Kidney Failure, Chronic; Hypertension; Blood Pressure; Denervation
PubMed: 38267652
DOI: 10.1007/s40292-023-00621-1