Leonie Dreher, Marlies Bode, Nicolas Ehnert, Catherine Meyer-Schwesinger, Thorsten Wiech, Jörg Köhl, Tobias B Huber, Tilo Freiwald, Georg R Herrnstadt, Ulrich O Wenzel
Backround: Complement activation may facilitate hypertension through its effects on immune responses. The anaphylatoxin C5a, a major inflammatory effector, binds to the C5a receptors 1 and 2 (C5aR1, C5aR2). We have recently shown that C5aR1-/- mice have reduced hypertensive renal injury. The role of C5aR2 in hypertension is unknown.
Methods: For examination of C5aR2 expression on infiltrating and resident renal cells a tandem dye Tomato-C5aR2 knock-in reporter mouse was used. Human C5aR2 expression was analyzed in a single-cell RNAseq data set from the kidneys of hypertensive patients. Finally, we examined the effect of angiotensin II-induced hypertension in C5aR2-deficient mice.
Results: Flow cytometric analysis of leukocytes isolated from kidneys of the reporter mice showed that dendritic cells are the major C5aR2-expressing population (34%) followed by monocyte/macrophages (30%) and neutrophils (14%). Using confocal microscopy C5aR2 was not detected in resident renal or cardiac cells. In the human kidney, C5aR2 was also mainly found in monocytes, macrophages, and dendritic cells with a significantly higher expression in hypertension (P < 0.05). Unilateral nephrectomy was performed followed by infusion of Ang II (0.75 ng/g/min) and a high salt diet in wildtype (n = 18) and C5aR2-deficient mice (n = 14). Blood pressure, renal injury (albuminuria, glomerular filtration rate, glomerular and tubulointerstitial injury, inflammation), and cardiac injury (cardiac fibrosis, heart weight, gene expression) did not differ between hypertensive wildtype and C5aR2-/- mice.
Conclusions: In summary, C5aR2 is mainly expressed in myeloid cells in the kidney in mice and humans but its deficiency has no effect on Ang II-induced hypertensive injury.
背景:补体激活可通过对免疫反应的影响促进高血压。C5a是一种主要的炎症效应物质,可与C5a受体1和2(C5aR1、C5aR2)结合。我们最近发现,C5aR1-/-小鼠的高血压肾损伤有所减轻。C5aR2在高血压中的作用尚不清楚:方法:使用串联染料 Tomato-C5aR2 基因敲入报告小鼠来检测 C5aR2 在浸润和驻留肾细胞中的表达。在高血压患者肾脏的单细胞 RNAseq 数据集中分析了人类 C5aR2 的表达。最后,我们研究了 C5aR2 基因缺陷小鼠对 Ang II 诱导的高血压的影响:从报告小鼠肾脏分离的白细胞流式细胞分析显示,树突状细胞是主要的 C5aR2 表达群体(34%),其次是单核/巨噬细胞(30%)和中性粒细胞(14%)。使用共聚焦显微镜在常驻肾脏或心脏细胞中未检测到 C5aR2。在人类肾脏中,C5aR2 也主要存在于单核细胞、巨噬细胞和树突状细胞中,在高血压中的表达量明显更高(pConclusion):总之,C5aR2 主要在小鼠和人类肾脏的髓样细胞中表达,但其缺乏对 Ang II 诱导的高血压损伤没有影响。
{"title":"Role of the Anaphylatoxin Receptor C5aR2 in Angiotensin II-Induced Hypertension and Hypertensive End-Organ Damage.","authors":"Leonie Dreher, Marlies Bode, Nicolas Ehnert, Catherine Meyer-Schwesinger, Thorsten Wiech, Jörg Köhl, Tobias B Huber, Tilo Freiwald, Georg R Herrnstadt, Ulrich O Wenzel","doi":"10.1093/ajh/hpae082","DOIUrl":"10.1093/ajh/hpae082","url":null,"abstract":"<p><strong>Backround: </strong>Complement activation may facilitate hypertension through its effects on immune responses. The anaphylatoxin C5a, a major inflammatory effector, binds to the C5a receptors 1 and 2 (C5aR1, C5aR2). We have recently shown that C5aR1-/- mice have reduced hypertensive renal injury. The role of C5aR2 in hypertension is unknown.</p><p><strong>Methods: </strong>For examination of C5aR2 expression on infiltrating and resident renal cells a tandem dye Tomato-C5aR2 knock-in reporter mouse was used. Human C5aR2 expression was analyzed in a single-cell RNAseq data set from the kidneys of hypertensive patients. Finally, we examined the effect of angiotensin II-induced hypertension in C5aR2-deficient mice.</p><p><strong>Results: </strong>Flow cytometric analysis of leukocytes isolated from kidneys of the reporter mice showed that dendritic cells are the major C5aR2-expressing population (34%) followed by monocyte/macrophages (30%) and neutrophils (14%). Using confocal microscopy C5aR2 was not detected in resident renal or cardiac cells. In the human kidney, C5aR2 was also mainly found in monocytes, macrophages, and dendritic cells with a significantly higher expression in hypertension (P < 0.05). Unilateral nephrectomy was performed followed by infusion of Ang II (0.75 ng/g/min) and a high salt diet in wildtype (n = 18) and C5aR2-deficient mice (n = 14). Blood pressure, renal injury (albuminuria, glomerular filtration rate, glomerular and tubulointerstitial injury, inflammation), and cardiac injury (cardiac fibrosis, heart weight, gene expression) did not differ between hypertensive wildtype and C5aR2-/- mice.</p><p><strong>Conclusions: </strong>In summary, C5aR2 is mainly expressed in myeloid cells in the kidney in mice and humans but its deficiency has no effect on Ang II-induced hypertensive injury.</p>","PeriodicalId":7578,"journal":{"name":"American Journal of Hypertension","volume":" ","pages":"810-825"},"PeriodicalIF":3.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Previous studies with several limitations have comparatively analyzed the relationship between ambulatory blood pressure (BP) and self-measured BP and biomarkers of organ damage. This study extends this line of research by examining the relationship between ambulatory and self-measured BP and cardiac, renal, and atherosclerotic biomarkers in outpatients at cardiovascular risk.
Methods: In 1,440 practice outpatients who underwent office, ambulatory, and self-measured BP monitoring, we assessed the relationships of each BP with organ damage biomarkers including b-type natriuretic peptide (BNP), echocardiographic left ventricular mass index (LVMI), urine albumin-creatinine ratio (UACR), and brachial-ankle pulse wave velocity (baPWV).
Results: In the comparison of correlation, self-measured systolic BP (SBP) was more strongly correlated to log-transformed (Ln) BNP (n = 1,435; r = 0.123 vs. r = -0.093, P < 0.001), LVMI (n = 1,278; r = 0.223 vs. r = 0.094, P < 0.001), Ln-UACR (n = 1,435; r = 0.244 vs. r = 0.154, P = 0.010), and baPWV (n = 1,360; r = 0.327 vs. r = 0.115, P < 0.001) than daytime ambulatory SBP. In the linear regression models including office, ambulatory, and self-measured SBP, only self-measured SBP was significantly related to Ln-BNP (P = 0.016) and LVMI (P < 0.001). In the logistic regression models for the top quartile of LVMI, adding self-measured SBP improved the model predictability (P = 0.027), but adding daytime ambulatory SBP did not. However, adding daytime ambulatory SBP improved the model predictability in the logistic model for the top quartile of baPWV including office and self-measured SBP (P = 0.030).
Conclusions: Our study findings suggested that self-measured BP was associated with cardiac biomarkers independent of ambulatory BP.
背景:以往的研究对非卧床血压(BP)和自我测量血压与器官损伤生物标志物之间的关系进行了比较分析,但存在一些局限性。本研究扩展了这一研究思路,研究了心血管风险门诊患者的动态血压和自测血压与心脏、肾脏和动脉粥样硬化生物标志物之间的关系:我们对 1440 名门诊患者进行了诊室、门诊和自测血压监测,评估了各血压与器官损伤生物标志物(包括 b 型钠尿肽 (BNP)、超声心动图左心室质量指数 (LVMI)、尿-白蛋白-肌酐比值 (UACR) 和肱踝脉搏波速度 (baPWV) 等)之间的关系:在相关性比较中,自我测量的收缩压(SBP)与对数转换(Ln)BNP(n=1,435;r=0.123 vs. r = -0.093,PC结论)的相关性更强:我们的研究结果表明,自测血压与心脏生物标志物相关,而与卧床血压无关。
{"title":"Relationships of Office, Ambulatory, and Self-measured Blood Pressure With Cardiac, Renal, and Atherosclerotic Biomarkers.","authors":"Keisuke Narita, Satoshi Hoshide, Kazuomi Kario","doi":"10.1093/ajh/hpae083","DOIUrl":"10.1093/ajh/hpae083","url":null,"abstract":"<p><strong>Background: </strong>Previous studies with several limitations have comparatively analyzed the relationship between ambulatory blood pressure (BP) and self-measured BP and biomarkers of organ damage. This study extends this line of research by examining the relationship between ambulatory and self-measured BP and cardiac, renal, and atherosclerotic biomarkers in outpatients at cardiovascular risk.</p><p><strong>Methods: </strong>In 1,440 practice outpatients who underwent office, ambulatory, and self-measured BP monitoring, we assessed the relationships of each BP with organ damage biomarkers including b-type natriuretic peptide (BNP), echocardiographic left ventricular mass index (LVMI), urine albumin-creatinine ratio (UACR), and brachial-ankle pulse wave velocity (baPWV).</p><p><strong>Results: </strong>In the comparison of correlation, self-measured systolic BP (SBP) was more strongly correlated to log-transformed (Ln) BNP (n = 1,435; r = 0.123 vs. r = -0.093, P < 0.001), LVMI (n = 1,278; r = 0.223 vs. r = 0.094, P < 0.001), Ln-UACR (n = 1,435; r = 0.244 vs. r = 0.154, P = 0.010), and baPWV (n = 1,360; r = 0.327 vs. r = 0.115, P < 0.001) than daytime ambulatory SBP. In the linear regression models including office, ambulatory, and self-measured SBP, only self-measured SBP was significantly related to Ln-BNP (P = 0.016) and LVMI (P < 0.001). In the logistic regression models for the top quartile of LVMI, adding self-measured SBP improved the model predictability (P = 0.027), but adding daytime ambulatory SBP did not. However, adding daytime ambulatory SBP improved the model predictability in the logistic model for the top quartile of baPWV including office and self-measured SBP (P = 0.030).</p><p><strong>Conclusions: </strong>Our study findings suggested that self-measured BP was associated with cardiac biomarkers independent of ambulatory BP.</p>","PeriodicalId":7578,"journal":{"name":"American Journal of Hypertension","volume":" ","pages":"769-776"},"PeriodicalIF":3.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marharyta Semenikhina, Roy O Mathew, Munsef Barakat, Justin P Van Beusecum, Daria V Ilatovskaya, Oleg Palygin
Hypertension (HTN) is one of the key global cardiovascular risk factors, which is tightly linked to kidney health and disease development. Podocytes, glomerular epithelial cells that play a pivotal role in maintenance of the renal filtration barrier, are significantly affected by increased glomerular capillary pressure in HTN. Damage or loss of these cells causes proteinuria, which marks the initiation of the HTN-driven renal damage. It goes without saying that effective BP management should not only mitigate cardiovascular risks but also preserve renal function by protecting podocyte integrity. This review offers a comprehensive examination of current blood pressure (BP) management strategies and their implications for podocyte structure and function and emphasizes strategies for the reduction of proteinuria in HTN. We explore primary and secondary antihypertensive agents, including ACE inhibitors, ARBs, calcium channel blockers, diuretics, as well as newer therapies (SGLT2 blocking and endothelin receptor antagonism), emphasizing their mechanistic roles in safeguarding podocytes and curtailing proteinuria.
{"title":"Blood pressure management strategies and podocyte health","authors":"Marharyta Semenikhina, Roy O Mathew, Munsef Barakat, Justin P Van Beusecum, Daria V Ilatovskaya, Oleg Palygin","doi":"10.1093/ajh/hpae120","DOIUrl":"https://doi.org/10.1093/ajh/hpae120","url":null,"abstract":"Hypertension (HTN) is one of the key global cardiovascular risk factors, which is tightly linked to kidney health and disease development. Podocytes, glomerular epithelial cells that play a pivotal role in maintenance of the renal filtration barrier, are significantly affected by increased glomerular capillary pressure in HTN. Damage or loss of these cells causes proteinuria, which marks the initiation of the HTN-driven renal damage. It goes without saying that effective BP management should not only mitigate cardiovascular risks but also preserve renal function by protecting podocyte integrity. This review offers a comprehensive examination of current blood pressure (BP) management strategies and their implications for podocyte structure and function and emphasizes strategies for the reduction of proteinuria in HTN. We explore primary and secondary antihypertensive agents, including ACE inhibitors, ARBs, calcium channel blockers, diuretics, as well as newer therapies (SGLT2 blocking and endothelin receptor antagonism), emphasizing their mechanistic roles in safeguarding podocytes and curtailing proteinuria.","PeriodicalId":7578,"journal":{"name":"American Journal of Hypertension","volume":"44 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142253790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sung Keun Park, Chang-Mo Oh, Jae-Hong Ryoo, Jo hyun chul, Eugene Kim, Ju Young Jung
Background Evidence has indicated that nocturia is a clinical manifestation of adverse health conditions including cardiovascular diseases and metabolic disorders. However, published data is less available for the clinical implication of nocturia on the development of hypertension. Method Study participants were 32,420 working aged Korean (21,355 men and 11,065 women) who periodically received health check-up. They were categorized into four groups by the frequency of nocturia (never, <1/week, 1-2/week, and ≥3/week). We used Cox proportional hazards models to analyze the multivariable-adjusted hazard ratio (HR) and 95% confidence intervals (CI) for incident hypertension (multivariable adjusted HR [95% CI]) in relation to the frequency of nocturia. Subgroup analysis was conducted by gender and sleep quality (good and poor sleep quality). Results In women, nocturia was associated with the increased risk of hypertension, compared with never nocturia (HR (95% CI); never: reference, <1/week: 1.33 [1.10 – 1.60], 1-2/week: 1.26 [1.00 – 1.58], and ≥3/week: 1.34 [1.05 – 1.72]). This association was not observed in men (HR (95% CI); never: reference, <1/week: 1.00 [0.93 – 1.08], 1-2/week: 1.00 [0.88 – 1.12], and ≥3/week: 1.06 [0.94 – 1.23]). In subgroup analysis by sleep quality, only women with good sleep quality showed the association between nocturia and the risk of hypertension However, women with poor sleep quality and men didn’t show the association between the frequency of nocturia and the risk of hypertension. Conclusion Nocturia is a potential risk factor for incident hypertension in working aged women with good sleep quality.
{"title":"The clinical implication of nocturia in predicting hypertension among working aged Koreans","authors":"Sung Keun Park, Chang-Mo Oh, Jae-Hong Ryoo, Jo hyun chul, Eugene Kim, Ju Young Jung","doi":"10.1093/ajh/hpae116","DOIUrl":"https://doi.org/10.1093/ajh/hpae116","url":null,"abstract":"Background Evidence has indicated that nocturia is a clinical manifestation of adverse health conditions including cardiovascular diseases and metabolic disorders. However, published data is less available for the clinical implication of nocturia on the development of hypertension. Method Study participants were 32,420 working aged Korean (21,355 men and 11,065 women) who periodically received health check-up. They were categorized into four groups by the frequency of nocturia (never, &lt;1/week, 1-2/week, and ≥3/week). We used Cox proportional hazards models to analyze the multivariable-adjusted hazard ratio (HR) and 95% confidence intervals (CI) for incident hypertension (multivariable adjusted HR [95% CI]) in relation to the frequency of nocturia. Subgroup analysis was conducted by gender and sleep quality (good and poor sleep quality). Results In women, nocturia was associated with the increased risk of hypertension, compared with never nocturia (HR (95% CI); never: reference, &lt;1/week: 1.33 [1.10 – 1.60], 1-2/week: 1.26 [1.00 – 1.58], and ≥3/week: 1.34 [1.05 – 1.72]). This association was not observed in men (HR (95% CI); never: reference, &lt;1/week: 1.00 [0.93 – 1.08], 1-2/week: 1.00 [0.88 – 1.12], and ≥3/week: 1.06 [0.94 – 1.23]). In subgroup analysis by sleep quality, only women with good sleep quality showed the association between nocturia and the risk of hypertension However, women with poor sleep quality and men didn’t show the association between the frequency of nocturia and the risk of hypertension. Conclusion Nocturia is a potential risk factor for incident hypertension in working aged women with good sleep quality.","PeriodicalId":7578,"journal":{"name":"American Journal of Hypertension","volume":"35 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bin Mao, Yide Yang, Zehui Fan, Yuxian Li, Wanyun Xiang, Bin Dong, Jie Hu
Background: This study aims to explore the association between a healthy lifestyle and abnormal ambulatory blood pressure (ABP) in Chinese youths.
Methods: A school-based sample of 1,296 college students was investigated. A lifestyle score was calculated by synthesizing 5 lifestyle factors, including smoking, alcohol consumption, diet, physical activity, and sleeping. The total score ranged from 0 to 5, with a higher score indicating a healthier lifestyle. This score was then divided into 3 categories representing low adherence to a healthy lifestyle (0-2), medium adherence (3), and high adherence (4-5). Abnormal 24-hour blood pressure (BP) was defined as systolic BP (SBP) ≥ 130 mm Hg and/or diastolic BP (DBP) ≥ 80 mm Hg. Abnormal daytime BP was determined as daytime SBP ≥ 135 mm Hg and/or DBP ≥ 85 mm Hg, while abnormal nighttime BP was characterized as nighttime SBP ≥ 120 mm Hg and/or DBP ≥ 70 mm Hg. We assessed the associations using the binomial regression model.
Results: Mean age was 18.81 years, and 74.5% were women. The prevalence of abnormal 24-hour BP, daytime BP, and nighttime BP are 4.2%, 3.7%, and 9.0%, respectively. We found that participants with a high level of adherence to a healthy lifestyle had a significantly lower prevalence of abnormal 24-hour BP [prevalence ratios (PR) = 0.15, 95% CI: 0.05, 0.48] and abnormal daytime BP (PR = 0.16, 95%CI: 0.05, 0.52), when compared to those with a low level of adherence and after adjusting for the potential covariates.
Conclusions: A healthier lifestyle is associated with a better ambulatory BP profile among youths.
{"title":"Association of a Healthy Lifestyle With Ambulatory 24-Hour Blood Pressure Among Chinese Youths: A Cross-Sectional Study.","authors":"Bin Mao, Yide Yang, Zehui Fan, Yuxian Li, Wanyun Xiang, Bin Dong, Jie Hu","doi":"10.1093/ajh/hpae074","DOIUrl":"10.1093/ajh/hpae074","url":null,"abstract":"<p><strong>Background: </strong>This study aims to explore the association between a healthy lifestyle and abnormal ambulatory blood pressure (ABP) in Chinese youths.</p><p><strong>Methods: </strong>A school-based sample of 1,296 college students was investigated. A lifestyle score was calculated by synthesizing 5 lifestyle factors, including smoking, alcohol consumption, diet, physical activity, and sleeping. The total score ranged from 0 to 5, with a higher score indicating a healthier lifestyle. This score was then divided into 3 categories representing low adherence to a healthy lifestyle (0-2), medium adherence (3), and high adherence (4-5). Abnormal 24-hour blood pressure (BP) was defined as systolic BP (SBP) ≥ 130 mm Hg and/or diastolic BP (DBP) ≥ 80 mm Hg. Abnormal daytime BP was determined as daytime SBP ≥ 135 mm Hg and/or DBP ≥ 85 mm Hg, while abnormal nighttime BP was characterized as nighttime SBP ≥ 120 mm Hg and/or DBP ≥ 70 mm Hg. We assessed the associations using the binomial regression model.</p><p><strong>Results: </strong>Mean age was 18.81 years, and 74.5% were women. The prevalence of abnormal 24-hour BP, daytime BP, and nighttime BP are 4.2%, 3.7%, and 9.0%, respectively. We found that participants with a high level of adherence to a healthy lifestyle had a significantly lower prevalence of abnormal 24-hour BP [prevalence ratios (PR) = 0.15, 95% CI: 0.05, 0.48] and abnormal daytime BP (PR = 0.16, 95%CI: 0.05, 0.52), when compared to those with a low level of adherence and after adjusting for the potential covariates.</p><p><strong>Conclusions: </strong>A healthier lifestyle is associated with a better ambulatory BP profile among youths.</p>","PeriodicalId":7578,"journal":{"name":"American Journal of Hypertension","volume":" ","pages":"674-681"},"PeriodicalIF":3.2,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: In the hypothalamic paraventricular nucleus (PVN) of spontaneously hypertensive rats (SHRs), the expression of the testis-specific protein, Y-encoded-like 2 (TSPYL2) and the phosphorylation level of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) are higher comparing with the normotensive Wistar Kyoto rats (WKY). But how they are involved in hypertension remains unclear. TSPYL2 may interact with JAK2/STAT3 in PVN to sustain high blood pressure during hypertension.
Methods: Knockdown of TSPYL2 via adeno-associated virus (AAV) carrying shRNA was conducted through bilateral microinjection into the PVN of SHR and WKY rats. JAK2/STAT3 inhibition was achieved by intraperitoneally or PVN injection of AG490 into the SHRs. Blood pressure (BP), plasma norepinephrine (NE), PVN inflammatory response, and PVN oxidative stress were measured.
Results: TSPYL2 knock-down in the PVN of SHRs but not WKYs led to reduced BP and plasma NE, deactivation of JAK2/STAT3, decreased expression of pro-inflammatory cytokine IL-1β, and increased expression of anti-inflammatory cytokine IL-10 in the PVN. Meanwhile, AG490 administrated in both ways reduced the BP in the SHRs and deactivated JAK2/STAT3 but failed to change the expression of TSPYL2 in PVN. AG490 also downregulated expression of IL-1β and upregulated expression of IL-10. Both knockdown of TSPYL2 and inhibition of JAK2/STAT3 can reduce the oxidative stress in the PVN of SHRs.
Conclusion: JAK2/STAT3 is regulated by TSPYL2 in the PVN of SHRs, and PVN TSPYL2/JAK2/STAT3 is essential for maintaining high BP in hypertensive rats, making it a potential therapeutic target for hypertension.
{"title":"Testis-Specific Protein, Y-Encoded-Like 2 Activates JAK2/STAT3 Pathway in Hypothalamic Paraventricular Nucleus to Sustain Hypertension.","authors":"Ying Li, Yang-Fei Xu, Hong-Li Chi, Jia-Yue Yu, Ya-Nan Gao, Hong-Bao Li, Yu-Ming Kang, Xiao-Jing Yu","doi":"10.1093/ajh/hpae067","DOIUrl":"10.1093/ajh/hpae067","url":null,"abstract":"<p><strong>Background: </strong>In the hypothalamic paraventricular nucleus (PVN) of spontaneously hypertensive rats (SHRs), the expression of the testis-specific protein, Y-encoded-like 2 (TSPYL2) and the phosphorylation level of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) are higher comparing with the normotensive Wistar Kyoto rats (WKY). But how they are involved in hypertension remains unclear. TSPYL2 may interact with JAK2/STAT3 in PVN to sustain high blood pressure during hypertension.</p><p><strong>Methods: </strong>Knockdown of TSPYL2 via adeno-associated virus (AAV) carrying shRNA was conducted through bilateral microinjection into the PVN of SHR and WKY rats. JAK2/STAT3 inhibition was achieved by intraperitoneally or PVN injection of AG490 into the SHRs. Blood pressure (BP), plasma norepinephrine (NE), PVN inflammatory response, and PVN oxidative stress were measured.</p><p><strong>Results: </strong>TSPYL2 knock-down in the PVN of SHRs but not WKYs led to reduced BP and plasma NE, deactivation of JAK2/STAT3, decreased expression of pro-inflammatory cytokine IL-1β, and increased expression of anti-inflammatory cytokine IL-10 in the PVN. Meanwhile, AG490 administrated in both ways reduced the BP in the SHRs and deactivated JAK2/STAT3 but failed to change the expression of TSPYL2 in PVN. AG490 also downregulated expression of IL-1β and upregulated expression of IL-10. Both knockdown of TSPYL2 and inhibition of JAK2/STAT3 can reduce the oxidative stress in the PVN of SHRs.</p><p><strong>Conclusion: </strong>JAK2/STAT3 is regulated by TSPYL2 in the PVN of SHRs, and PVN TSPYL2/JAK2/STAT3 is essential for maintaining high BP in hypertensive rats, making it a potential therapeutic target for hypertension.</p>","PeriodicalId":7578,"journal":{"name":"American Journal of Hypertension","volume":" ","pages":"682-691"},"PeriodicalIF":3.2,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"New Kids on the Hypertension Block: Novel Agents With New Mechanisms of Action.","authors":"Ernesto L Schiffrin","doi":"10.1093/ajh/hpae051","DOIUrl":"https://doi.org/10.1093/ajh/hpae051","url":null,"abstract":"","PeriodicalId":7578,"journal":{"name":"American Journal of Hypertension","volume":"37 9","pages":"651-653"},"PeriodicalIF":3.2,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141974840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}