Cardiovascular Disease and Its Association With Histological Changes of the Left Stellate Ganglion

Mounting evidence has demonstrated that the autonomic system plays a role in the morbidity and mortality of certain cardiovascular disease states. Ventricular arrhythmias have been associated with the level of sympathetic activation. We attempted to determine if the presence of fibrosis, a marker for previous ischemic events, correlates with an increase in the number of left stellate ganglion nerve cell bodies which is indicative of hypersympathetic stimulation to the myocardial tissue. Left stellate ganglia were removed, sectioned and prepared using hematoxylin and eosin and Masson’s trichrome stain. The interventricular septum of the heart corresponding to the stellate ganglion samples were removed, serially sectioned, and stained with hematoxylin and eosin and Masson’s trichrome stain. The samples were described using a grading scale to quantify the percentage of fibrosis. Ganglion nerve cell bodies were then individually counted in three separate high-powered fields. A student’s T-test was used to statistically evaluate the data. Stellate ganglions were sampled from 32 cadavers. Fibrosis was present within 72% (23/32) of the interventricular septums that were sampled. Nine interventricular septums were found to be free of fibrosis. For those interventricular septums that were positive for the presence of fibrosis, the mean left stellate ganglion nerve cell bodies was 39.8 (Range: 26–51). For those interventricular septums that were negative for the presence of fibrosis, the mean left stellate ganglion nerve cell bodies was 34.3 (Range: 27–46). The difference between the mean nerve cell bodies for interventricular septums with fibrosis and without fibrosis was found to be statistically significant (P = 0.048). Histological changes in terms of the number of left stellate ganglion nerve cell bodies seem to be dependent upon the presence of fibrosis within the interventricular septum. Considering fibrosis of the interventricular septum is a marker for previous ischemic events, an increase in the number of nerve cell bodies of the left stellate ganglion in the presence of fibrosis suggests an association does exist between hypersympathetic stimulation to the myocardial tissue and myocardial infarction. Further research into this association is warranted in order to determine if left stellate ganglion blockade is a viable treatment option for arrhythmias following myocardial infarctions

CXCL4 in undifferentiated connective tissue disease at risk for systemic sclerosis (SSc) (previously referred to as very early SSc)

The aim of the study was to evaluate CXCL4 levels in undifferentiated connective tissue disease at risk for SSc (UCTD-SSc-risk) and confirm its increase and investigate its prognostic value. Serum CXCL4 levels were measured in 45 patients and 24 controls. CXCL4 was significantly higher in UCTD-SSc-risk patients than in controls. It resulted higher in patients with a shorter disease duration and in those lacking capillaroscopic alterations. We confirm that CXCL4 levels are increased in UCTD-risk-SSc patients. Further studies are needed to investigate the role of CXCL4 assessment in UCTD-risk-SSc

The Role of Neuropathy Screening Tools in Patients Affected by Fibromyalgia

Fibromyalgia syndrome (sFM) is one of the most common causes of chronic pain. This study aimed to assess the presence of small and large fiber impairment in fibromyalgic patients by applying validated scores used in the screening for diabetic neuropathy. The endpoints for the study were the assessment of neuropathy prevalence in sFM patients using the NerveCheck Master (NCM), the Michigan Neuropathy Screening Instrument (MNSI), the Diabetic Neuropathy Symptom (DNS) and the Douleur Neuropathique 4 Questions (DN4). The sample was composed of 46 subjects: subjects with sFM (n = 23) and healthy controls (HC) (n = 23). The positivity rates in each group for DN4 were significantly different (p < 0.001), with a prevalence in symptomatic subjects of 56.3% (n = 9) among sFM individuals. A similar difference was also observed with the DNS total score (p < 0.001). NCM and MNSI did not disclose significant differences between the two groups. This finding seems to confirm the data regarding the prevalence of a neuropathic pain in sFM patients

Cardiac Hypertrophy: from Pathophysiological Mechanisms to Heart Failure Development

Cardiac hypertrophy develops in response to increased workload to reduce ventricular wall stress and maintain function and efficiency. Pathological hypertrophy can be adaptive at the beginning. However, if the stimulus persists, it may progress to ventricular chamber dilatation, contractile dysfunction, and heart failure, resulting in poorer outcome and increased social burden. The main pathophysiological mechanisms of pathological hypertrophy are cell death, fibrosis, mitochondrial dysfunction, dysregulation of Ca2+-handling proteins, metabolic changes, fetal gene expression reactivation, impaired protein and mitochondrial quality control, altered sarcomere structure, and inadequate angiogenesis. Diabetic cardiomyopathy is a condition in which cardiac pathological hypertrophy mainly develop due to insulin resistance and subsequent hyperglycaemia, associated with altered fatty acid metabolism, altered calcium homeostasis and inflammation. In this review, we summarize the underlying molecular mechanisms of pathological hypertrophy development and progression, which can be applied in the development of future novel therapeutic strategies in both reversal and prevention

An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors

Sodium-glucose co-transporter 2 (SGLT2) inhibitors block glucose reabsorption in the renal proximal tubule, an insulin-independent mechanism that plays a critical role in glycemic regulation in diabetes. In addition to their glucose-lowering effects, SGLT2 inhibitors prevent both renal damage and the onset of chronic kidney disease and cardiovascular events, in particular heart failure with both reduced and preserved ejection fraction. These unexpected benefits prompted changes in treatment guidelines and scientific interest in the underlying mechanisms. Aside from the target effects of SGLT2 inhibition, a wide spectrum of beneficial actions is described for the kidney and the heart, even though the cardiac tissue does not express SGLT2 channels. Correction of cardiorenal risk factors, metabolic adjustments ameliorating myocardial substrate utilization, and optimization of ventricular loading conditions through effects on diuresis, natriuresis, and vascular function appear to be the main underlying mechanisms for the observed cardiorenal protection. Additional clinical advantages associated with using SGLT2 inhibitors are antifibrotic effects due to correction of inflammation and oxidative stress, modulation of mitochondrial function, and autophagy. Much research is required to understand the numerous and complex pathways involved in SGLT2 inhibition. This review summarizes the current known mechanisms of SGLT2-mediated cardiorenal protection

Metabolomic fingerprinting of renal disease progression in Bardet-Biedl syndrome reveals mitochondrial dysfunction in kidney tubular cells.

Chronic kidney disease (CKD) is a major clinical sign of patients with Bardet-Biedl syndrome (BBS), especially in those carrying BBS10 mutations. Twenty-nine patients with BBS and 30 controls underwent a serum-targeted metabolomic analysis. In vitro studies were conducted in two kidney-derived epithelial cell lines, where Bbs10 was stably deleted (IMCD3-Bbs10-/-cells) and over-expressed. The CKD status affected plasmatic metabolite fingerprinting in both patients with BBS and controls. Specific phosphatidylcholine and acylcarnitines discriminated eGFR decline only in patients with BBS. IMCD3-Bbs10-/ cells displayed intracellular lipidaccumulation, reduced mitochondrial potential membrane and citrate synthase staining. Mass-Spectrometry-based analysis revealed that human BBS10 interacted with six mitochondrial proteins, in vitro. In conclusion, renal dysfunction correlated with abnormal phosphatidylcholine and acylcarnitines plasma levels in patients with BBS; in vitro, Bbs10 depletion caused mitochondrial defects while human BBS10 interacted with several mitochondria-related proteins, suggesting an unexplored role of this protein