Regulation of DNA methylation and 2-OG/TET signaling by choline alleviated cardiac hypertrophy in spontaneously hypertensive rats.

DNA methylation is a well-defined epigenetic modification that regulates gene transcription. However, the role of DNA methylation in the cardiac hypertrophy seen in hypertension is unclear. This study was performed to investigate genome-wide DNA methylation profiles in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKY), and the cardioprotective effect of choline. Eight-week-old male SHRs received intraperitoneal injections of choline (8 mg/kg/day) for 8 weeks. SHRs showed aberrant methylation distribution on chromosomes and genome regions, with decreased methylation levels at CHG and CHH sites. A total of 91,559 differentially methylated regions (DMRs) were detected between SHRs and WKY rats, of which 28,197 were demethylated and 63,362 were methylated. Choline treatment partly restored the DMRs in SHRs, which were related to 131 genes. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis of DMRs suggested that choline partly reversed the dysfunctions of biological processes, cellular components and molecular functions in SHRs. Moreover, the inhibition of 2-oxoglutarate accumulation by choline, thereby inhibiting excessive activation of ten-eleven translocation methylcytosine dioxygenase enzymes, may correlate with the beneficial effects of choline on methylation levels, cardiac hypertrophy and cardiac function of SHRs, as indicated by decreased heart rate and blood pressure, and increased ejection fraction and fractional shortening. This study provides the first genome-wide DNA methylation profile of the hypertrophic myocardium of SHRs and suggests a novel role for this epigenetic modification in hypertension. Choline treatment may represent a promising approach for modification of DNA methylation and optimization of the epigenetic profile for antihypertensive therapy.

Pyridostigmine regulates glucose metabolism and mitochondrial homeostasis to reduce myocardial vulnerability to injury in diabetic mice.

Diabetic patients are more susceptible to myocardial ischemia damage than nondiabetic patients, with worse clinical outcomes and greater mortality. The mechanism may be related to glucose metabolism, mitochondrial homeostasis, and oxidative stress. Pyridostigmine may improve vagal activity to protect cardiac function in cardiovascular diseases. Researchers have not determined whether pyridostigmine regulates glucose metabolism and mitochondrial homeostasis to reduce myocardial vulnerability to injury in diabetic mice. In the present study, autonomic imbalance, myocardial damage, mitochondrial dysfunction, and oxidative stress were exacerbated in isoproterenol-stimulated diabetic mice, revealing the myocardial vulnerability of diabetic mice to injury compared with mice with diabetes or exposed to isoproterenol alone. Compared with normal mice, the expression of glucose transporters (GLUT)1/4 phosphofructokinase (PFK) FB3, and pyruvate kinase isoform (PKM) was decreased in diabetic mice, but increased in isoproterenol-stimulated normal mice. Following exposure to isoproterenol, the expression of (GLUT)1/4 phosphofructokinase (PFK) FB3, and PKM decreased in diabetic mice compared with normal mice. The downregulation of SIRT3/AMPK and IRS-1/Akt in isoproterenol-stimulated diabetic mice was exacerbated compared with that in diabetic mice or isoproterenol-stimulated normal mice. Pyridostigmine improved vagus activity, increased GLUT1/4, PFKFB3, and PKM expression, and ameliorated mitochondrial dysfunction and oxidative stress to reduce myocardial damage in isoproterenol-stimulated diabetic mice. Based on these results, it was found that pyridostigmine may reduce myocardial vulnerability to injury via the SIRT3/AMPK and IRS-1/Akt pathways in diabetic mice with isoproterenol-induced myocardial damage. This study may provide a potential therapeutic target for myocardial damage in diabetic patients.

[Recent progress on obesity-induced myocardial remodeling and its possible mechanism of mitochondrial dyshomeostasis].

Obesity is an important risk factor for cardiovascular diseases, which can lead to a variety of cardiovascular diseases including myocardial remodeling. Obesity may induce myocardial dysfunction by affecting hemodynamics, inducing autonomic imbalance, adipose tissue dysfunction, and mitochondrial dyshomeostasis. The key necessary biochemical functions for metabolic homeostasis are performed in mitochondria, and mitochondrial homeostasis is considered as one of the key determinants for cell viability. Mitochondrial homeostasis is regulated by dynamic regulation of mitochondrial fission and fusion, as well as mitochondrial cristae remodeling, biogenesis, autophagy, and oxidative stress. The mitochondrial fission-fusion and morphological changes of mitochondrial cristae maintain the integrity of the mitochondrial structure. The mitochondria maintain a "healthy" state by balancing biogenesis and autophagy, while reactive oxygen species can act as signaling molecules to regulate intracellular signaling. The excessive accumulation of lipids and lipid metabolism disorder in obesity leads to mitochondrial dyshomeostasis, which activate the apoptotic cascade and lead to myocardial remodeling. In this review, we provide an overview of the recent research progress on obesity-induced myocardial remodeling and its possible mechanism of mitochondrial dyshomeostasis.

Pyridostigmine protects against cardiomyopathy associated with adipose tissue browning and improvement of vagal activity in high-fat diet rats.

Obesity, a major contributor to the development of cardiovascular diseases, is associated with an autonomic imbalance characterized by sympathetic hyperactivity and diminished vagal activity. Vagal activation plays important roles in weight loss and improvement of cardiac function. Pyridostigmine is a reversible acetylcholinesterase inhibitor, but whether it ameliorates cardiac lipid accumulation and cardiac remodeling in rats fed a high-fat diet has not been determined. This study investigated the effects of pyridostigmine on high-fat diet-induced cardiac dysfunction and explored the potential mechanisms. Rats were fed a normal or high-fat diet and treated with pyridostigmine. Vagal discharge was evaluated using the BL-420S system, and cardiac function by echocardiograms. Lipid deposition and cardiac remodeling were determined histologically. Lipid utility was assessed by qPCR. A high-fat diet led to a significant reduction in vagal discharge and lipid utility and a marked increase in lipid accumulation, cardiac remodeling, and cardiac dysfunction. Pyridostigmine improved vagal activity and lipid metabolism disorder and cardiac remodeling, accompanied by an improvement of cardiac function in high-fat diet-fed rats. An increase in the browning of white adipose tissue in pyridostigmine-treated rats was also observed and linked to the expression of UCP-1 and CIDEA. Additionally, pyridostigmine facilitated activation of brown adipose tissue via activation of the SIRT-1/AMPK/PGC-1α pathway. In conclusion, a high-fat diet resulted in cardiac lipid accumulation, cardiac remodeling, and a significant decrease in vagal discharge. Pyridostigmine ameliorated cardiomyopathy, an effect related to reduced cardiac lipid accumulation, and facilitated the browning of white adipose tissue while activating brown adipose tissue.

Acetylcholine attenuated TNF-α-induced intracellular Ca2+ overload by inhibiting the formation of the NCX1-TRPC3-IP3R1 complex in human umbilical vein endothelial cells.

The endoplasmic reticulum (ER) forms discrete junctions with the plasma membrane (PM) that play a critical role in the regulation of Ca2+ signaling during cellular bioenergetics, apoptosis and autophagy. We have previously confirmed that acetylcholine can inhibit ER stress and apoptosis after inflammatory injury. However, limited research has focused on the effects of acetylcholine on ER-PM junctions. In this work, we evaluated the structure and function of the supramolecular sodium-calcium exchanger 1 (NCX1)-transient receptor potential canonical 3 (TRPC3)-inositol 1,4,5-trisphosphate receptor 1 (IP3R1) complex, which is involved in regulating Ca2+ homeostasis during inflammatory injury. The width of the ER-PM junctions of human umbilical vein endothelial cells (HUVECs) was measured in nanometres using transmission electron microscopy and a fluorescent probe for Ca2+. Protein-protein interactions were assessed by immunoprecipitation. Ca2+ concentration was measured using a confocal microscope. An siRNA assay was employed to silence specific proteins. Our results demonstrated that the peripheral ER was translocated to PM junction sites when induced by tumour necrosis factor-alpha (TNF-α) and that NCX1-TRPC3-IP3R1 complexes formed at these sites. After down-regulating the protein expression of NCX1 or IP3R1, we found that the NCX1-mediated inflow of Ca2+ and the release of intracellular Ca2+ stores were reduced in TNF-α-treated cells. We also observed that acetylcholine attenuated the formation of NCX1-TRPC3-IP3R1 complexes and maintained calcium homeostasis in cells treated with TNF-α. Interestingly, the positive effects of acetylcholine were abolished by the selective M3AChR antagonist darifenacin and by AMPK siRNAs. These results indicate that acetylcholine protects endothelial cells from TNF-alpha-induced injury, [Ca2+]cyt overload and ER-PM interactions, which depend on the muscarinic 3 receptor/AMPK pathway, and that acetylcholine may be a new inhibitor for suppressing [Ca2+]cyt overload.

Long-term administration of pyridostigmine attenuates pressure overload-induced cardiac hypertrophy by inhibiting calcineurin signalling.

Cardiac hypertrophy is associated with autonomic imbalance, characterized by enhanced sympathetic activity and withdrawal of parasympathetic control. Increased parasympathetic function improves ventricular performance. However, whether pyridostigmine, a reversible acetylcholinesterase inhibitor, can offset cardiac hypertrophy induced by pressure overload remains unclear. Hence, this study aimed to determine whether pyridostigmine can ameliorate pressure overload-induced cardiac hypertrophy and identify the underlying mechanisms. Rats were subjected to either sham or constriction of abdominal aorta surgery and treated with or without pyridostigmine for 8 weeks. Vagal activity and cardiac function were determined using PowerLab. Cardiac hypertrophy was evaluated using various histological stains. Protein markers for cardiac hypertrophy were quantitated by Western blot and immunoprecipitation. Pressure overload resulted in a marked reduction in vagal discharge and a profound increase in cardiac hypertrophy index and cardiac dysfunction. Pyridostigmine increased the acetylcholine levels by inhibiting acetylcholinesterase in rats with pressure overload. Pyridostigmine significantly attenuated cardiac hypertrophy based on reduction in left ventricular weight/body weight, suppression of the levels of atrial natriuretic peptide, brain natriuretic peptide and ß-myosin heavy chain, and a reduction in cardiac fibrosis. These effects were accompanied by marked improvement of cardiac function. Additionally, pyridostigmine inhibited the CaN/NFAT3/GATA4 pathway and suppressed Orai1/STIM1 complex formation. In conclusion, pressure overload resulted in cardiac hypertrophy, cardiac dysfunction and a significant reduction in vagal discharge. Pyridostigmine attenuated cardiac hypertrophy and improved cardiac function, which was related to improved cholinergic transmission efficiency (decreased acetylcholinesterase and increased acetylcholine), inhibition of the CaN/NFAT3/GATA4 pathway and suppression of the interaction of Orai1/STIM1.

[Recent progress of mitochondrial quality control in ischemic heart disease and its role in cardio-protection of vagal nerve].

Ischemic heart disease (IHD) is the life-threatening cardiovascular disease. Mitochondria have emerged as key participants and regulators of cellular energy demands and signal transduction. Mitochondrial quality is controlled by a number of coordinated mechanisms including mitochondrial fission, fusion and mitophagy, which plays an important role in maintaining healthy mitochondria and cardiac function. Recently, dysfunction of each process in mitochondrial quality control has been observed in the ischemic hearts. This review describes the mechanism of mitochondrial dynamics and mitophagy as well as its performance linked to myocardial ischemia. Moreover, in combination with our study, we will discuss the effect of vagal nerve on mitochondria in cardio-protection.

[Role of endoplasmic reticulum-plasma membrane junctions in intracellular calcium homeostasis and cardiovascular disease].

Calcium overload is one of the important mechanisms of cardiovascular disease. Endoplasmic reticulum is an important organelle which regulates intracellular calcium homeostasis by uptake, storage and mobilization of calcium. So it plays a critical role in regulation of intracellular calcium homeostasis. Endoplasmic reticulum, which is widely distributed in cytoplasm, has a large number of membrane junction sites. Recent studies have reported that these junction sites are distributed on plasma membrane and organelle membranes (mitochondria, lysosomes, Golgi apparatus, etc.), separately. They could form complexes to regulate calcium transport. In this review, we briefly outlined the recent research progresses of endoplasmic reticulum-plasma membrane junctions in intracellular calcium homeostasis and cardiovascular disease, which may offer a new strategy for prevention and treatment of cardiovascular disease.

[Research Progress of Immunity Mechanism in Hypertension].

Hypertension, which can cause a variety of cardiovascular and cerebrovascular complications, is a serious threat to human health. Currently, it is found that hypertension is related to immunoregulatory abnormality, which could lead to chronic inflammation. Then the chronic inflammation may impair vascular endothelial function and activate renin-angiotensin system, which cause vascular remodeling, angiosclerosis, dysfunctional vasoconstriction and vasodilatation, and exacerbate hypertension. The immunoregulatory abnormality of hypertension involves macrophage infiltration of the organization, the dendritic cell of antigen presentation and natural killer cells of activation in nonspecific immunity and activation of T cells in specific immune. The key of immunity mechanism of hypertension is the Toll like receptor to activate immune system and lead to inflammation. Autonomic nervous system is also closely related to the development and progression of hypertension. Autonomic imbalance in hypertension leads to immunoregulatory abnormality, cardiovascular injury, and dysfunctional vasoconstriction and vasodilatation, which ultimately results in exacerbation of hypertension. Therefore, research on neuro-immune regulation will help to provide novel strategies for therapy of hypertension. In this review, we will provide an overview of the research progress of the immunity mechanism of hypertension and the regulation of immune system by the autonomic nervous system.

An efficient strategy to syntheses of isoflavones.

Isoflavones were synthesized by two steps in good yields, starting from commercially available 2-hydroxyacetophenones and benzene analogs. First, intermediate 3-(dimethylamino)-1-(2-hydroxyphenyl) prop-2-en-1-ones were obtained by the condensation of 2-hydroxyacetophenones and DMF-DMA in DMF with high yields. Second, isoflavones were synthesized by irradiation of 3-(dimethylamino)-1-(2-hydroxyphenyl)prop- 2-en-1-ones in the presence of iodine using benzene analogs as solvent under a mercury lamp.

Prevalence of Suboptimal Health Status and Its Influencing Factors among Chinese Software Programmers.

BACKGROUND: There is a lack of specific study of the suboptimal health status (SHS) in software programmers. The aims of the present study were to investigate the prevalence of SHS and analyze the influencing factors among Chinese software programmers. METHODS: A cross-sectional survey using a programmer SHS scale was conducted to evaluate the prevalence of SHS, as well chi-square test and multi-factor logistic regression were applied to analyze the relationship between suboptimal health and personal basic information, living and work habits in software programmers. RESULTS: The prevalence of SHS was 18.67% in software programmers. Single factor analysis found that there were differences in suboptimal health prevalence among different work cities (P = 0.031), hours of sleep per day (P = 0.046), overtime days per month (P = 0.010) and exercise frequency per week (P = 0.015). The factors for suboptimal health such as hours of sleep per day (OR = 0.307, 95% CI = 0.096∼0.984) and exercise frequency per week (OR = 0.190, 95% CI = 0.054∼0.671) significantly affected subjects of SHS via multi-factor logistic regression analysis, indicating that adequate sleep and exercise decreased the chance of SHS up to 30.70% and 19.00%, respectively. CONCLUSION: Suboptimal health had become a serious public health challenge in Chinese software programmers. Whilst, the health status of the programmers could be effectively elevated by improving lifestyles.

Push or Pull Electrons: Acetoxy and Carbomethoxy-Substituted Isomerisms in Organic Solar Cell Acceptors.

Isomerism is a major factor affecting the properties of materials. Herein, two isomeric acceptors based on acetoxy and methyl ester end group substituents, BTIC-OCOMe and BTIC-COOMe are reported. When blended with PBDB-TF, devices based on BTIC-OCOMe achieve an inferior (8.32%) power conversion efficiency (PCE) while the BTIC-COOMe material has a superior PCE of 13.25%. We investigated the reasons why these two devices, which differ only in the isomeric substituents on the terminal site, have such a large difference in photovoltaic performance. Our investigation conducted theoretical calculations and examined UV-vis absorption, energy levels, exciton dissociation and bimolecular recombination, mobilities tests, photoluminescence, and packing modes. It is found that the energy levels of the materials are fine-tuned, the absorption spectra are adjusted, and the energy loss is regulated. Our studies explored the reasons for the properties of materials differing, and the acetoxy and carbomethoxy substitutions provided some useful information concerning high-performance acceptor materials.

Nanographene-Osmapentalyne Complexes as a Cathode Interlayer in Organic Solar Cells Enhance Efficiency over 18.

Interface engineering is a critical method by which to efficiently enhance the photovoltaic performance of nonfullerene solar cells (NFSC). Herein, a series of metal-nanographene-containing large transition metal involving dπ -pπ conjugated systems by way of the addition reactions of osmapentalynes and p-diethynyl-hexabenzocoronenes is reported. Conjugated extensions are engineered to optimize the π-conjugation of these metal-nanographene molecules, which serve as alcohol-soluble cathode interlayer (CIL) materials. Upon extension of the π-conjugation, the power conversion efficiency (PCE) of PM6:BTP-eC9-based NFSCs increases from 16% to over 18%, giving the highest recorded PCE. It is deduced by X-ray crystallographic analysis, interfacial contact methods, morphology characterization, and carrier dynamics that modification of hexabenzocoronenes-styryl can effectively improve the short-circuit current density (Jsc ) and fill factor of organic solar cells (OSCs), mainly due to the strong and ordered charge transfer, more matching energy level alignments, better interfacial contacts between the active layer and the electrodes, and regulated morphology. Consequently, the carrier transport is largely facilitated, and the carrier recombination is simultaneously impeded. These new CIL materials are broadly able to enhance the photovoltaic properties of OSCs in other systems, which provides a promising potential to serve as CILs for higher-quality OSCs.

Prognostic significance of peritumoural and intratumoural budding in intestinal-type gastric adenocarcinoma.

BACKGROUND AND STUDY AIMS: Tumour budding (TB) at the invasive front, termed peritumoural budding (PTB), is an established prognostic factor for many solid tumours. However, intratumoural budding (ITB) in gastric adenocarcinoma (GAC), which is frequently observed at the tumour centre, particularly in tumour biopsy tissues, remains poorly understood. Hence, we aimed to determine the correlation of ITB with PTB and their connection with clinicopathological characteristics as well as their prognostic value in GAC. PATIENTS AND METHODS: We investigated a total of 153 cases of GAC wherein tissues were primarily resected and their related clinicopathological data. A continuous series of paraffin-embedded tissues was stained by haematoxylin-eosin staining, and budding cells were identified by immunohistochemical staining. PTB and ITB were counted in five fields with the highest density of tumour buds. The selected area was examined under 40 high-power field. Cases were divided into low-grade TB and high-grade TB groups according to the median bud count. RESULTS: Among the 153 patients with GAC, 51 underwent simultaneous observation of ITB and PTB, which were found to have a significant positive correlation. A higher grade of ITB in tumours was associated with positive lymph node metastasis and could predict a worse prognosis. Additionally, patients with simultaneous PTB and ITB had a shorter overall survival than those with PTB alone, suggesting a worse prognosis. CONCLUSION: PTB and ITB were found to be adverse prognostic factors and high-risk indicators of intestinal-type GAC, and ITB plays an important role in evaluating GAC prognosis in gastroscopic biopsy tissues. Additionally, TB might become a useful index for predicting GAC prognosis in the future.

Addition of alkynes and osmium carbynes towards functionalized dπ-pπ conjugated systems.

The metal-carbon triple bonds and carbon-carbon triple bonds are both highly unsaturated bonds. As a result, their reactions tend to afford cycloaddition intermediates or products. Herein, we report a reaction of M≡C and C≡C bonds that affords acyclic addition products. These newly discovered reactions are highly efficient, regio- and stereospecific, with good functional group tolerance, and are robust under air at room temperature. The isotope labeling NMR experiments and theoretical calculations reveal the reaction mechanism. Employing these reactions, functionalized dπ-pπ conjugated systems can be easily constructed and modified. The resulting dπ-pπ conjugated systems were found to be good electron transport layer materials in organic solar cells, with power conversion efficiency up to 16.28% based on the PM6: Y6 non-fullerene system. This work provides a facile, efficient methodology for the preparation of dπ-pπ conjugated systems for use in functional materials.

Pharmacological Modulation of Vagal Nerve Activity in Cardiovascular Diseases.

Cardiovascular diseases are life-threatening illnesses with high morbidity and mortality. Suppressed vagal (parasympathetic) activity and increased sympathetic activity are involved in these diseases. Currently, pharmacological interventions primarily aim to inhibit over-excitation of sympathetic nerves, while vagal modulation has been largely neglected. Many studies have demonstrated that increased vagal activity reduces cardiovascular risk factors in both animal models and human patients. Therefore, the improvement of vagal activity may be an alternate approach for the treatment of cardiovascular diseases. However, drugs used for vagus nerve activation in cardiovascular diseases are limited in the clinic. In this review, we provide an overview of the potential drug targets for modulating vagal nerve activation, including muscarinic, and ß-adrenergic receptors. In addition, vagomimetic drugs (such as choline, acetylcholine, and pyridostigmine) and the mechanism underlying their cardiovascular protective effects are also discussed.

Carrier Dynamics and Morphology Regulated by 1,8-Diiodooctane in Chlorinated Nonfullerene Polymer Solar Cells.

Very small amounts of 1,8-diiodooctane (DIO) are very effective at optimizing the performance of polymer solar cells (PSCs). To date, the underlying influences are not yet fully understood, especially in nonfullerene PSCs. Herein, the influence of DIO on carrier dynamics and morphology in the PBDBT2Cl:IT4F system was investigated in detail. We combined the characterization of the transient dynamics with the morphology characterization of PSC devices to explore the origin of enhanced performance. Compared to the cast device, the champion device with 0.5% DIO revealed the maximum of current density ( Jsc) and fill factor (FF). The optimum DIO content helps to enhance carrier transport and optimize morphology, while excess DIO produces adverse effects due to the induced intense aggregation and dilated size in blend films. The results provide some hints of improved device performance upon using DIO as an additive in nonfullerene PSCs.

Cholinergic drugs ameliorate endothelial dysfunction by decreasing O-GlcNAcylation via M3 AChR-AMPK-ER stress signaling.

AIMS: Obesity is associated with increased cardiovascular morbidity and mortality. It is accompanied by augmented O-linked ß-N-acetylglucosamine (O-GlcNAc) modification of proteins via increasing hexosamine biosynthetic pathway (HBP) flux. However, the changes and regulation of the O-GlcNAc levels induced by obesity are unclear. MAIN METHODS: High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh). KEY FINDINGS: PYR significantly reduced body weight, blood glucose, and O-GlcNAcylation levels and attenuated vascular endothelial cells detachment in HFD-fed mice. HG addition induced endoplasmic reticulum (ER) stress and increased O-GlcNAcylation levels and apoptosis in HUVECs in a time-dependent manner. Additionally, HG decreased levels of phosphorylated AMP-activated protein kinase (AMPK). Interestingly, ACh significantly blocked damage to HUVECs induced by HG. Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor). Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh. SIGNIFICANCE: Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.

Choline ameliorates cardiovascular damage by improving vagal activity and inhibiting the inflammatory response in spontaneously hypertensive rats.

Autonomic dysfunction and abnormal immunity lead to systemic inflammatory responses, which result in cardiovascular damage in hypertension. The aim of this report was to investigate the effects of choline on cardiovascular damage in hypertension. Eight-week-old male spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats were intraperitoneally injected with choline or vehicle (8 mg/kg/day). After 8 weeks, choline restored the cardiac function of the SHRs, as evidenced by decreased heart rate, systolic blood pressure, left ventricle systolic pressure, and ±dp/dtmax and increased ejection fraction and fractional shortening. Choline also ameliorated the cardiac hypertrophy of the SHRs, as indicated by reduced left ventricle internal dimensions and decreased cardiomyocyte cross-sectional area. Moreover, choline improved mesenteric arterial function and preserved endothelial ultrastructure in the SHRs. Notably, the protective effect of choline may be due to its anti-inflammatory effect. Choline downregulated expression of interleukin (IL)-6 and tumour necrosis factor-α and upregulated IL-10 in the mesenteric arteries of SHRs, possibly because of the inhibition of Toll-like receptor 4. Furthermore, choline restored baroreflex sensitivity and serum acetylcholine level in SHRs, thus indicating that choline improved vagal activity. This study suggests that choline elicits cardiovascular protective effects and may be useful as a potential adjunct therapeutic approach for hypertension.