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Revue Medicale Suisse Jan 2024Highlights for 2023 include the confirmation of hypertension as a cardiovascular risk factor and the standard procedure for measuring blood pressure. Transdermal...
Highlights for 2023 include the confirmation of hypertension as a cardiovascular risk factor and the standard procedure for measuring blood pressure. Transdermal oestrogens do not appear to be associated with an increased risk of hypertension unlike oestrogen given orally. The usefulness of blood pressure measured in hospital in elderly patients and the risks of intensive treatment are reviewed. A new study suggests that we are not all equal when it comes to recommended treatments. Finally, RNA interference technology has enabled the synthesis of a new antihypertensive treatment administered every 6 months that inhibits the production of hepatic angiotensinogen with a good effect on blood pressure.
Topics: Aged; Humans; Hypertension; Blood Pressure; Antihypertensive Agents; Hospitals; Technology
PubMed: 38299956
DOI: 10.53738/REVMED.2024.20.859.252 -
Pain Jul 2024Visceral pain is a leading cause of morbidity in inflammatory bowel disease (IBD), contributing significantly to reduced quality of life. Currently available analgesics...
Visceral pain is a leading cause of morbidity in inflammatory bowel disease (IBD), contributing significantly to reduced quality of life. Currently available analgesics often lack efficacy or have intolerable side effects, driving the need for a more complete understanding of the mechanisms causing pain. Whole transcriptome gene expression analysis was performed by bulk RNA sequencing of colonic biopsies from patients with ulcerative colitis (UC) and Crohn's disease (CD) reporting abdominal pain and compared with noninflamed control biopsies. Potential pronociceptive mediators were identified based on gene upregulation in IBD biopsy tissue and cognate receptor expression in murine colonic sensory neurons. Pronociceptive activity of identified mediators was assessed in assays of sensory neuron and colonic afferent activity. RNA sequencing analysis highlighted a 7.6-fold increase in the expression of angiotensinogen transcripts, Agt , which encode the precursor to angiotensin II (Ang II), in samples from UC patients ( P = 3.2 × 10 -8 ). Consistent with the marked expression of the angiotensin AT 1 receptor in colonic sensory neurons, Ang II elicited an increase in intracellular Ca 2+ in capsaicin-sensitive, voltage-gated sodium channel subtype Na V 1.8-positive sensory neurons. Ang II also evoked action potential discharge in high-threshold colonic nociceptors. These effects were inhibited by the AT 1 receptor antagonist valsartan. Findings from our study identify AT 1 receptor-mediated colonic nociceptor activation as a novel pathway of visceral nociception in patients with UC. This work highlights the potential utility of angiotensin receptor blockers, such as valsartan, as treatments for pain in IBD.
Topics: Humans; Animals; Inflammatory Bowel Diseases; Angiotensin II; Mice; Male; Gene Expression Profiling; Female; Colon; Sensory Receptor Cells; Adult; Middle Aged; Mice, Inbred C57BL; Nociceptors; Transcriptome
PubMed: 38293826
DOI: 10.1097/j.pain.0000000000003159 -
Food & Function Feb 2024Green tea polyphenol (-)-Epigallocatechin-3-gallate (EGCG) has been well studied for its biological activities in the prevention of chronic diseases. However, the...
Green tea polyphenol (-)-Epigallocatechin-3-gallate (EGCG) has been well studied for its biological activities in the prevention of chronic diseases. However, the biological activities of EGCG oxidation-derived polymers remain unclear. Previously, we found that these polymers accumulated in intraperitoneal tissues after intraperitoneal injection and gained an advantage over native EGCG in increasing insulin sensitivity regulating the renin-angiotensin system (RAS) in type 2 diabetic mice. The present study determined the pro-apoptosis activities and anticancer mechanisms of the EGCG oxidation-derived polymer preparation (the >10 kDa EGCG polymers) in digestive tract cancer cells. Upon incubation of the >10 kDa EGCG polymers with CaCo2 colon cancer cells, these polymers coated the cell surface and regulated multiple components of the RAS in favor of cancer inhibition, including the downregulation of angiotensin-converting enzyme (ACE), angiotensin-II (AngII) and AngII receptor type 1 (AT1R) in the pro-tumor axis, as well as the upregulation of angiotensin-converting enzyme 2 (ACE2) and angiotensin1-7 (Ang(1-7)) in the anti-tumor axis. The treatment also markedly increased angiotensinogen (AGT), which is the precursor of the angiotensin peptides. The regulation of these RAS components occurred prior to apoptosis. Similar pro-apoptotic mechanisms of the >10 kDa EGCG polymers, were also observed in TCA8113 oral cancer cells. The >10 kDa EGCG polymers exhibited compromised activities in scavenging or initiating reactive oxygen species compared to EGCG, but gained a higher reactivity toward sulfhydryl groups, including protein cysteine thiols. We propose that the polymers bind onto the cell surface and regulate multiple RAS components by reacting with the sulfhydryl groups on the ectodomains of transmembrane proteins.
Topics: Humans; Mice; Animals; Renin-Angiotensin System; Diabetes Mellitus, Experimental; Caco-2 Cells; Angiotensin II; Apoptosis; Gastrointestinal Tract; Neoplasms; Catechin
PubMed: 38293823
DOI: 10.1039/d3fo03795a -
JNMA; Journal of the Nepal Medical... Nov 2023Chronic lithium toxicity is a potentially serious side effect on patients taking lithium for a prolonged period with the diagnosis of mood disorders. The toxicity is...
UNLABELLED
Chronic lithium toxicity is a potentially serious side effect on patients taking lithium for a prolonged period with the diagnosis of mood disorders. The toxicity is even higher in patients taking drugs that interfere with the metabolism of lithium like angiotensin receptor blockers and in older patients with reduced kidney function. In this report, we present the case of a 62-year-old woman who presented to the emergency department with symptoms including loose stools, generalised body weakness, slurred speech, coarse hand tremors, and dystonia persisting for fifteen days. She had been under lithium therapy for bipolar type 1 disorder for 15 years before experiencing these symptoms, which emerged shortly after the addition of telmisartan (angiotensinogen receptor blocker) for hypertension.
KEYWORDS
angiotensin receptor blocker; bipolar disorder; case reports; lithium; telmisartan.
Topics: Female; Humans; Aged; Middle Aged; Lithium; Angiotensin Receptor Antagonists; Telmisartan; Bipolar Disorder; Antidepressive Agents
PubMed: 38289730
DOI: 10.31729/jnma.8346 -
International Journal of Immunogenetics Apr 2024To investigate the correlation between susceptibility to systemic lupus erythematosus (SLE) and single nucleotide polymorphisms (SNPs) rs699, rs4762 and rs1926723 in the...
To investigate the correlation between susceptibility to systemic lupus erythematosus (SLE) and single nucleotide polymorphisms (SNPs) rs699, rs4762 and rs1926723 in the AGT gene in the population of Northeast China, while also introducing a new method for early detection of SLE. A total of 856 cases of SLE patients and healthy volunteers who attended the First Affiliated Hospital of Harbin Medical University from January 2020 to December 2022 were recruited. Clinical information and biood samples were collected from particpants in this study. SNaPshot sequencing technology was used to sequence the bases of the rs699, rs4762 and rs1926723 in the AGT gene. The genetic stability of SNPs was analysed by means of Hardy-Weinberg (HWE) genetic equilibrium. The study examined the correlation between genetically stable SNPs and susceptibility to SLE using logistic regression analysis. Rs699 did not adhere to the principles of the HWE genetic equilibrium (p < .01). Conversely, both rs4762 and rs1926723 conformed to the HWE genetic equilibrium (p > .05). However, no significant differences in genotypes and alleles frequencies of the rs4762 were observed between the two groups (p > .05). Furthermore, there was a significant difference in the distribution of AG, GG genotypes frequency and G allele frequency at the rs1926723 between the two groups (p < .001). Individuals with AG and GG genotypes and the G allele had a significantly lower frequency of SLE, indicating a potential genetic protective factor against susceptibility to the SLE. The SNPs rs1926723 may be linked to the susceptibility to SLE, and the AG, GG genotypes and the G allele may be important protective factors for the development of SLE in Northeast China.
Topics: Humans; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; Lupus Erythematosus, Systemic; Genotype; Gene Frequency; China; Case-Control Studies
PubMed: 38265173
DOI: 10.1111/iji.12655 -
Cureus Dec 2023Teratogenic agents have been shown to have drastic and detrimental effects on fetuses if exposed to the agent during uterine life. The most sensitive time for a... (Review)
Review
Teratogenic agents have been shown to have drastic and detrimental effects on fetuses if exposed to the agent during uterine life. The most sensitive time for a developing fetus is during the first trimester, and teratogenic exposure during this time can lead to severe deformities in the fetus. The Food and Drug Administration has categorized teratogenic agents based on the severity of their effect on the fetus; these categories include A, B, C, D, and X. Category A is the safest, with the most dangerous, and highly contraindicated in pregnant patients being Category X. This review article will discuss the teratogenic agents leflunomide, isotretinoin, thalidomide, warfarin, tetracycline, and angiotensinogen-converting enzyme inhibitors. Leflunomide can cause cranioschisis, exencephaly, and vertebral, head, and limb malformations. Isotretinoin's main teratogenic effects include central nervous system malformations, hydrocephalus, eye abnormalities, cardiac septal defects, thymus abnormalities, spontaneous abortions, and external ear abnormalities. Thalidomide has been shown to cause limb deformities, bowel atresia, and heart defects when the embryo is exposed to the agent during development. Warfarin can lead to spontaneous abortion and intrauterine death, as well as nasal hypoplasia, hypoplasia of extremities, cardiac defects, scoliosis, and mental retardation when exposed in utero. Tetracycline's teratogenic effects include gastrointestinal distress, esophageal ulceration and strictures, teeth discoloration, hepatotoxicity, and calcifications. Angiotensinogen-converting enzyme inhibitors can cause skull hyperplasia, anuria, hypotension, renal failure, lung hypoplasia, skeletal deformation, oligohydramnios, and fetal death. Teratogenic effects can be avoided if the pregnant patient is educated on the teratogenic effects of these agents.
PubMed: 38222129
DOI: 10.7759/cureus.50465 -
International Journal of Molecular... Jan 2024Increased body weight (BW) induces inappropriate renin-angiotensin system (RAS) activation. The activation of the intrarenal RAS is associated with increased urinary...
Increased body weight (BW) induces inappropriate renin-angiotensin system (RAS) activation. The activation of the intrarenal RAS is associated with increased urinary angiotensinogen (uAGT), blood pressure (BP), and kidney damage. Here, we examined uAGT excretion levels in young non-diabetic human subjects with overweight (OW) and non-diabetic mice with high-fat diet (HFD)-induced OW. Human subjects (women and men; 20-28 years old) included two groups: (a) overweight (OW, = 17, BMI ≥ 25); and (b) controls (normal weight (NW; = 26, BMI ≤ 25). In these subjects, we measured BP, albuminuria, and protein levels of uAGT by ELISA adjusted by urinary creatinine (expressed by uAGT/uCrea). Mice (female and male C57BL/6J mice, 8 ± 2 weeks of age) also included two groups: HFD or normal fat diet (NFD) fed for 8 weeks. We measured BW, fasting blood glucose (FBG), BP by telemetry, albuminuria, and uAGT by ELISA. In humans: (i) no significant changes were observed in BP, albuminuria, and FBG when comparing NW and OW subjects; (ii) multivariate logistic regression analysis of independent predictors related to uAGT/uCrea levels demonstrated a strong association between uAGT and overweight; (iii) urinary reactive oxygen species (ROS) were augmented in men and women with OW; (iv) the uAGT/uCrea ratio was higher in men with OW. However, the uAGT/uCrea values were lower in women even with OW. In mice: (i) males fed an HFD for 8 weeks became OW while females did not; (ii) no changes were observed either in FBG, BP, or albuminuria; (iii) kidney ROS were augmented in OW male mice after 28 weeks but not in females; (iv) OW male mice showed augmented excretion of uAGT but this was undetectable in females fed either NFD or HFD. In humans and mice who are OW, the urinary excretion of AGT differs between males and females and overcomes overt albuminuria.
Topics: Adult; Animals; Female; Humans; Male; Mice; Young Adult; Albuminuria; Angiotensinogen; Mice, Inbred C57BL; Overweight; Reactive Oxygen Species; Sex Characteristics; Renin-Angiotensin System
PubMed: 38203807
DOI: 10.3390/ijms25010635 -
International Journal of Molecular... Dec 2023Small interfering RNA (siRNA) represents a novel, fascinating therapeutic strategy that allows for selective reduction in the production of a specific protein through... (Review)
Review
Small interfering RNA (siRNA) represents a novel, fascinating therapeutic strategy that allows for selective reduction in the production of a specific protein through RNA interference. In the cardiovascular (CV) field, several siRNAs have been developed in the last decade. Inclisiran has been shown to significantly reduce low-density lipoprotein cholesterol (LDL-C) circulating levels with a reassuring safety profile, also in older patients, by hampering proprotein convertase subtilisin/kexin type 9 (PCSK9) production. Olpasiran, directed against apolipoprotein(a) mRNA, prevents the assembly of lipoprotein(a) [Lp(a)] particles, a lipoprotein linked to an increased risk of ischemic CV disease and heart valve damage. Patisiran, binding transthyretin (TTR) mRNA, has demonstrated an ability to improve heart failure and polyneuropathy in patients with TTR amyloidosis, even in older patients with wild-type form. Zilebesiran, designed to reduce angiotensinogen secretion, significantly decreases systolic and diastolic blood pressure (BP). Thanks to their effectiveness, safety, and tolerability profile, and with a very low number of administrations in a year, thus overcoming adherence issues, these novel drugs are the leaders of a new era in molecular therapies for CV diseases.
Topics: Humans; Aged; Cardiovascular Diseases; Proprotein Convertase 9; Heart Failure; Hypertension; RNA, Small Interfering; Atherosclerosis; RNA, Messenger
PubMed: 38203499
DOI: 10.3390/ijms25010328 -
PloS One 2024Due to the inconsistent findings from various studies, the role of gene polymorphisms in the renin-angiotensin system in influencing the development of cardiomyopathy... (Meta-Analysis)
Meta-Analysis
Due to the inconsistent findings from various studies, the role of gene polymorphisms in the renin-angiotensin system in influencing the development of cardiomyopathy remains unclear. In this study, we conducted a systematic review and meta-analysis to summarize the findings regarding the impact of angiotensin converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T, and angiotensin II Type 1 receptor (AGTR1) A1166C gene polymorphisms in patients with cardiomyopathy. We performed a comprehensive search of several electronic databases, including PubMed, Embase, the Cochrane Library, and Web of Science, covering articles published from the time of database creation to April 17, 2023. Studies on the assessment of genetic polymorphisms in genes related to the renin-angiotensin system in relation to cardiomyopathy were included. The primary outcome was cardiomyopathy. Risk of bias was assessed using the Newcastle-Ottawa Scale scale. The meta-analysis includes 19 studies with 4,052 cases and 5,592 controls. The ACE I/D polymorphisms were found to be associated with cardiomyopathy (allelic model D vs I: OR = 1.29, 95CI% = 1.08-1.52; dominant model DD+ID vs II: OR = 1.43, 95CI% = 1.01-2.02; recessive model DD vs ID+II: OR = 0.79, 95CI% = 0.64-0.98). AGT M235T polymorphism and cardiomyopathy were not significantly correlated (allelic model T vs M: OR = 1.26, 95CI% = 0.96-1.66; dominant model TT+MT vs MM: OR = 1.30, 95CI% = 0.98-1.73; recessive model TT vs MT+MM: OR = 0.63, 95CI% = 0.37-1.07). AGTR1 polymorphism and cardiomyopathy were not significantly associated under allelic model A vs C (OR = 0.69, 95CI% = 0.46-1.03) and recessive model AA vs CA+CC (OR = 0.89, 95CI% = 0.34-2.30), but under the dominant model AA+CA vs CC (OR = 0.51, 95CI% = 0.38-0.68). The current meta-analysis reveals that polymorphisms in ACE I/D may be a genetic risk factor for cardiomyopathy. There is an association between AGTR1 gene polymorphisms and risk of cardiomyopathy under the specific model.
Topics: Humans; Renin-Angiotensin System; Risk Factors; Polymorphism, Genetic; Peptidyl-Dipeptidase A; Angiotensinogen; Cardiomyopathies; Receptor, Angiotensin, Type 1
PubMed: 38166133
DOI: 10.1371/journal.pone.0295626 -
Risk Management and Healthcare Policy 2023The renin-angiotensin system plays an important role in the central regulation of blood pressure (BP). Genetic variations of angiotensinogen (AGT) and angiotensin II...
PURPOSE
The renin-angiotensin system plays an important role in the central regulation of blood pressure (BP). Genetic variations of angiotensinogen (AGT) and angiotensin II type 1 receptor (AGTR1) may increase susceptibility to elevated BP and hypertension. This study investigated the effects of AGT rs699 and AGTR1 rs5186 single nucleotide polymorphisms (SNPs) on BP at baseline and at a 5-year follow-up.
PATICIPANTS AND METHODS
The study population consisted of participants from the Electricity Generating Authority of Thailand cohort study (n=354); data were collected at baseline (2013) and 5 years later (2018). Genotyping of the two SNPs was performed using TaqMan assay and statistical analyses were performed with SNPStats software.
RESULTS
The frequencies of the two SNPs were within the Hardy-Weinberg equilibrium (p=0.22 for AGT rs699 and p=0.06 for AGTR1 rs5186). For each SNP, mutant genotypes were significantly associated with increased systolic BP and/or diastolic BP in the codominant and recessive models. Risk alleles of AGT rs699 and AGTR1 rs5186 were associated with increased odds of hypertension and hypertension with metabolic syndrome at follow-up.
CONCLUSION
Overall, our results suggest that polymorphisms of genes in the renin-angiotensin system increase susceptibility to the development and progression of hypertension and the development of the metabolic syndrome.
PubMed: 38164294
DOI: 10.2147/RMHP.S442983