IF 2.9 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2026-01-01 DOI: 10.1016/j.peptides.2025.171463

Kun Xue , Junmei Yang , Jia Hu , Lingwei Kong , Xinguo Cui , Yang Kong

Background

Mitochondrial biogenesis is upregulated in glioblastoma to support tumor growth, invasion, and chemoresistance by meeting the heightened metabolic demands of cancer cells. Fibroblast growth factor 9 (FGF9) is a potent oncogenic driver in various cancers, promoting proliferation, survival, and angiogenesis. However, its role in regulating mitochondrial metabolism in glioblastoma remains unclear.

Methods

The activation of FGF9/fibroblast growth factor receptor 2 (FGFR2) signaling and expression of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α) were examined in clinical glioblastoma samples and cell lines using real-time PCR, immunohistochemistry, and western blotting. Mitochondrial biogenesis and function in FGF9-treated U-87 cells were evaluated by measuring relative mtDNA/nDNA ratio, mitochondrial mass (MitoTracker), complex activity, membrane potential, and ATP production. The role of cAMP response element-binding protein (CREB) signaling was investigated using the specific inhibitor H89.

Results

We found activated FGF9/FGFR2 signaling in glioblastoma patients, with elevated serum FGF9 and tumor FGFR2. PGC-1α was upregulated in samples and cell lines. FGF9 boosted mitochondrial biogenesis and function in U-87 cells, increasing mtDNA, mass, complex activity, membrane potential, and ATP production. Mechanistically, FGF9 promoted the expression of PGC-1α and mitochondrial transcription factor A (TFAM) via activation of CREB signaling. Inhibition of CREB phosphorylation by H89 abolished FGF9-induced upregulation of PGC-1α/TFAM, mtDNA replication, and ATP production.

Conclusion

These findings reveal that FGF9 enhances mitochondrial biogenesis in glioblastoma through the CREB-PGC-1α-TFAM axis, uncovering a novel metabolic mechanism underlying its pro-tumorigenic effects.

背景：线粒体生物发生在胶质母细胞瘤中上调，通过满足癌细胞的高代谢需求来支持肿瘤的生长、侵袭和化疗耐药。成纤维细胞生长因子9 （FGF9）在多种癌症中是一个强有力的致癌驱动因子，促进增殖、存活和血管生成。然而，其在胶质母细胞瘤中调节线粒体代谢的作用尚不清楚。方法：采用实时荧光定量PCR、免疫组织化学和western blotting检测临床胶质母细胞瘤样本和细胞系中FGF9/成纤维细胞生长因子受体2 （FGFR2）信号的激活和过氧化物酶体增殖体激活受体- γ辅助激活因子1- α (PGC-1α)的表达。通过测量相对mtDNA/nDNA比率、线粒体质量（MitoTracker）、复合物活性、膜电位和ATP生成，评估fgf9处理的U-87细胞的线粒体生物发生和功能。使用特异性抑制剂H89研究了cAMP反应元件结合蛋白（CREB）信号通路的作用。结果：我们在胶质母细胞瘤患者中发现激活的FGF9/FGFR2信号，血清FGF9和肿瘤FGFR2升高。PGC-1α在样品和细胞系中表达上调。FGF9促进了U-87细胞线粒体的生物发生和功能，增加了mtDNA、质量、复合物活性、膜电位和ATP的产生。机制上，FGF9通过激活CREB信号通路促进PGC-1α和线粒体转录因子A （TFAM）的表达。H89抑制CREB磷酸化可消除fgf9诱导的PGC-1α/TFAM、mtDNA复制和ATP产生的上调。结论：这些发现揭示了FGF9通过CREB-PGC-1α-TFAM轴促进胶质母细胞瘤线粒体生物发生，揭示了其促肿瘤作用的新的代谢机制。

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引用次数: 0

Menstrual cycle phase and hormonal contraceptive use influence circulating proforms of atrial natriuretic peptide, adrenomedullin, and the vasopressin proxy copeptin in healthy women 月经周期阶段和激素避孕药的使用影响健康女性心房利钠肽、肾上腺髓质素和抗利尿素代理copeptin的循环形式

IF 2.9 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2026-01-01 DOI: 10.1016/j.peptides.2026.171465

Anne Sophie Broholt Jensen , Janne Gasseholm Bentzen , Jens P. Goetze , Mette Hansen , Tine Vrist Dam , Sara A. Christensen , Trine Pagh Ludvigsen , Michael Nyberg , Dijana Terzic

Background

Cardiovascular disease is the main cause of mortality among women. However, the menstrual cycle and hormonal contraception are often overlooked in research. This study investigates whether concentrations of common cardiovascular biomarkers (natriuretic peptides, adrenomedullin, and copeptin) change during a menstrual cycle and with hormonal contraception use.

Methods

Concentrations of cardiovascular biomarkers in 2 prospective cohorts were measured. In The Menstrual Cycle Study, blood samples were collected throughout a menstrual cycle, and in The Contraception Study, blood samples were collected from women using different contraceptive methods.

Results

Blood samples from 19 women (The Menstrual Cycle study) and 638 women (The Contraception Study) were analyzed. Concentrations of mid-regional (MR)-pro-atrial natriuretic peptide (proANP) are highest during the early follicular phase (Delta %: median: 111.5 %, IQR: 100.6–115.9 %) and lowest during the mid-luteal phase (median: 88.0 %, IQR: 80.4–103.2 %) (P = .02). When compared to women with natural cycles, median concentrations of MR-proANP were reduced by 19.3 % in those using combined oral contraceptives (COC)/vaginal contraceptive ring and by 18.2 % in progestin-users. Additionally, copeptin concentrations were reduced by 11.9 % in COC/vaginal contraceptive ring-users, while MR-proadrenomedullin (proADM) concentrations were reduced by 15.4 % in COC/vaginal contraceptive ring-users and 11.5 % in progestin-users compared to non-users.

Conclusions

MR-proANP concentrations vary across the menstrual cycle with the highest concentrations during the early follicular phase. Furthermore, concentrations of MR-proANP, copeptin, and MR-proADM are affected by hormonal contraception. Our findings underscore the necessity to consider menstrual cycle phases and use of hormonal contraception in clinical assessment of premenopausal women when using cardiovascular biomarkers.

背景：心血管疾病是妇女死亡的主要原因。然而，月经周期和激素避孕在研究中往往被忽视。本研究探讨了常见的心血管生物标志物（利钠肽、肾上腺髓质素和copeptin）的浓度是否在月经周期和使用激素避孕时发生变化。方法测量2个前瞻性队列的心血管生物标志物浓度。在月经周期研究中，采集了整个月经周期的血液样本，而在避孕研究中，采集了使用不同避孕方法的女性的血液样本。结果对19名女性（月经周期研究）和638名女性（避孕研究）的血液样本进行了分析。中区域(MR)-前房利钠肽（proANP）浓度在卵泡早期最高（δ %：中位数：111.5 %,IQR: 100.6-115.9 %），在黄体中期最低（中位数：88.0 %,IQR: 80.4-103.2 %）（P = .02）。与自然周期的妇女相比，使用联合口服避孕药(COC)/阴道避孕环的妇女MR-proANP的中位浓度降低了19.3% %，使用黄体酮的妇女MR-proANP的中位浓度降低了18.2% %。此外，COC/阴道避孕环使用者的copeptin浓度降低了11.9 %，而COC/阴道避孕环使用者的mr - pro肾上腺素（proADM）浓度与非使用者相比降低了15.4 %，孕激素使用者的proADM浓度降低了11.5 %。结论smr - proanp浓度随月经周期变化，卵泡早期浓度最高。此外，MR-proANP、copeptin和MR-proADM的浓度受激素避孕的影响。我们的研究结果强调了在使用心血管生物标志物对绝经前妇女进行临床评估时考虑月经周期和激素避孕的必要性。

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引用次数: 0

Oral salmon acylated ghrelin increases food intake in common carp (Cyprinus carpio) via ghrelin receptors, likely through sensory nerves rather than systemic absorption 口服鲑鱼酰化的胃饥饿素通过胃饥饿素受体增加鲤鱼（鲤）的食物摄入量，可能是通过感觉神经而不是全身吸收。

IF 2.9 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2026-01-01 DOI: 10.1016/j.peptides.2026.171464

Minoru Kihara , Teppei Yamagiwa , Hidekazu Katayama , Hiroyuki Kaiya

This study clarified the local mechanism of action and assessed the aquaculture potential of orally administered salmon acylated ghrelin (sAG) on feed intake in common carp (Cyprinus carpio). Experimental diets containing sAG (ranging from 0.001 to 13.04 µg/g) were prepared and fed to carp at 2.0 % of body weight (BW) in single-shot trials. Fish receiving diets of 0.64 µg/g (1.3 µg/100 g BW) or higher exhibited a significant, dose-dependent increase in additional feed intake, plateauing at 1.20 µg/g (2.4 µg/100 g BW). Despite this behavioral effect, plasma ghrelin levels remained unchanged, as measured by both N-terminal and salmon-specific C-terminal radioimmunoassays, confirming that sAG was not systemically absorbed. The orexigenic effect was abolished by pretreatment with the ghrelin receptor antagonist [D-Lys3]-GHRP-6 or with capsaicin, demonstrating local sAG action via growth hormone secretagogue receptor signaling and peripheral sensory neurons (likely vagal afferents). These findings provide the first evidence that fish ghrelin exerts biological activity via a non-circulatory neuroendocrine pathway. This advances our understanding of the vertebrate gut–brain axis and highlights the potential of harnessing locally acting peptides for physiological modulation in aquatic species.

本研究阐明了口服鲑鱼酰化胃饥饿素（sAG）对鲤鱼采食量的局部作用机制，并评价了其在水产养殖中的潜力。制备含sAG 0.001 ~ 13.04µg/g的试验饲料，饲喂体重为2.0%的鲤鱼。饲料中添加0.64µg/g（1.3µg/100g BW）或更高水平的鱼，其额外采食量呈剂量依赖性显著增加，稳定在1.20µg/g（2.4µg/100g BW）。尽管存在这种行为效应，但血浆胃饥饿素水平保持不变，通过n端和鲑鱼特异性c端放射免疫测定，证实了sAG没有被全身吸收。促生长素受体拮抗剂[D-Lys3]-GHRP-6或辣椒素预处理可消除厌氧效应，表明局部sAG通过生长激素促分泌受体信号传导和外周感觉神经元（可能是迷走神经传入神经）起作用。这些发现提供了鱼类胃饥饿素通过非循环神经内分泌途径发挥生物活性的第一个证据。这促进了我们对脊椎动物肠脑轴的理解，并突出了利用局部作用肽进行水生物种生理调节的潜力。

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引用次数: 0

Thymosin beta 4: An emerging therapeutic candidate for kidney diseases 胸腺素β 4：一种新的肾脏疾病治疗候选药物。

IF 2.9 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2026-01-01 DOI: 10.1016/j.peptides.2026.171467

Huajie Di , Jiaxin Huang , Dexin Zhang, Fei Ni, Rui Zheng, Hongquan Geng

Over the past decades, the escalating global burden of kidney disease has underscored an urgent need for innovative therapeutic strategies. Thymosin β4 (Tβ4), a highly conserved 43-amino-acid peptide encoded by the X-linked TMSB4x gene, is the predominant β-thymosin in mammalian cells and a multifunctional regulator of cellular homeostasis. Once considered mainly an actin-sequestering molecule, Tβ4 and its N-terminal metabolite N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP) now emerge as dynamic mediators of renal injury and repair. In this review, we synthesize current evidence on the Tβ4–Ac-SDKP axis. We map intra- and extracellular mechanisms and relevant signaling pathways, delineate cell-type and spatial expression across glomerular and tubular compartments, and critically evaluate its renoprotective efficacy—including cytoprotection, anti-inflammatory and antifibrotic actions—across models of acute and chronic kidney injury. To reconcile disparate findings, we propose conceptual frameworks that consider bidirectional effects on fibrosis and model-dependent mechanisms. Finally, translational opportunities are appraised with attention to pharmacokinetics, peptide stability and delivery strategies. Key challenges moving forward include validating efficacy in additional clinically relevant models, overcoming peptide instability and completing comprehensive safety assessments.

在过去的几十年里，肾脏疾病的全球负担不断增加，迫切需要创新的治疗策略。胸腺素β4 （Thymosin β4, Tβ4）是一种高度保守的43个氨基酸肽，由x连锁的TMSB4x基因编码，是哺乳动物细胞中主要的β-胸腺素，是细胞稳态的多功能调节剂。曾被认为主要是一种肌动蛋白隔离分子的t - β4及其n端代谢物n-乙酰基- ser - asp - lys - pro （Ac-SDKP）现在被认为是肾脏损伤和修复的动态介质。在这篇综述中，我们综合了目前关于t - β4- ac - sdkp轴的证据。我们绘制了细胞内和细胞外机制以及相关的信号通路，描绘了肾小球和小管间室的细胞类型和空间表达，并在急性和慢性肾损伤模型中批判性地评估了其肾保护功效，包括细胞保护、抗炎和抗纤维化作用。为了调和不同的发现，我们提出了考虑纤维化双向效应和模型依赖机制的概念框架。最后，通过药物动力学、肽稳定性和递送策略来评估翻译机会。未来的主要挑战包括验证其他临床相关模型的有效性，克服肽不稳定性和完成全面的安全性评估。

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引用次数: 0

Non-peptide bradykinin B2 receptor ligands possessing the substituted quinolinyl moiety: Pharmacological properties and prospective clinical uses 具有取代喹啉基部分的非肽缓激肽B2受体配体：药理学性质和前瞻性临床应用。

IF 2.9 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2026-01-01 DOI: 10.1016/j.peptides.2026.171466

Ahmed Sahli , René C.-Gaudreault , François Marceau

Bradykinin is a nonapeptide derived from the cleavage of circulating kininogens by plasma or tissue kallikreins and is endowed with powerful pharmacologic actions, such as the production of protein-rich exudates and vasodilation. The widely expressed B2 receptor for bradykinin (a G protein-coupled receptor) has been the focus of intense drug development efforts for more than 4 decades, with marked differences in affinities and competitiveness for synthetic antagonists across mammalian species. Many non-peptide ligands of the human B2 receptor have been developed by various industrial organizations. A recurring substituted 8-[(2,6-dichlorophenyl)methoxy]-2-methylquinolinyl ("quinolyl") moiety, or variants thereof, was explored by several pharmaceutical organizations. FR173657, fasitibant, anatibant, deucrictibant and Compound 3 (the non-deuterated version of deucrictibant) are examples of competitive antagonists of the human B2 receptor, some of which having reached the stage of clinical trials. Other compounds structurally related to the common moiety, such as FR190997 and Compound 47a, are partial or nearly full agonists of the B2 receptor. The ongoing clinical development of deucrictibant for the treatment of hereditary angioedema is a first step in clarifying the therapeutic potential of orally bioavailable B2 receptor antagonists.

缓激肽是一种非肽，由血浆或组织激肽酶裂解循环激原而产生，具有强大的药理作用，如产生富含蛋白质的渗出物和血管舒张。广泛表达的缓激肽B2受体（一种G蛋白偶联受体）已成为近40年来药物开发的焦点，在哺乳动物物种中，合成拮抗剂的亲和力和竞争力存在显著差异。许多人类B2受体的非肽配体已经被各种工业组织开发出来。重复取代的8-[（2,6-二氯苯基）甲氧基]-2-甲基喹啉基（“喹啉基”）部分，或其变体，已被几个制药组织探索。FR173657、fasitibant、anatibant、deucricbant和化合物3 （deucricbant的非氘化版本）是人类B2受体竞争拮抗剂的例子，其中一些已进入临床试验阶段。其他结构上与共同片段相关的化合物，如FR190997和化合物47a，是B2受体的部分或几乎完全激动剂。正在进行的用于治疗遗传性血管性水肿的去氧剂的临床开发是阐明口服生物可利用的B2受体拮抗剂治疗潜力的第一步。

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引用次数: 0

Distinct and complementary metabolic effects of GLP-1 and glucagon receptor agonism in diet-induced obese mice GLP-1和胰高血糖素受体激动作用在饮食诱导的肥胖小鼠中不同和互补的代谢作用。

IF 2.9 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-12-20 DOI: 10.1016/j.peptides.2025.171462

Marie Winther-Sørensen , Christine Rasmussen , Samuel A.J. Trammell , Caroline Hansen , Mogens Vyberg , Reza Serizawa , Erik A. Richter , Trisha J. Grevengoed , Lise Lotte Gluud , Rune E. Kuhre , Nicolai J. Wewer Albrechtsen

Glucagon-like peptide-1 (GLP-1) and glucagon receptor co-agonism is an emerging therapeutic strategy for obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). To examine their distinct and combined metabolic actions in a model reflecting chronic disease, we used diet-induced obese mice that had been maintained on high-fat diet from early adulthood, allowing obesity and hepatic steatosis to develop gradually and remain stable before initiating treatment. Mice received a long-acting GLP-1 receptor agonist (NNC2220), a long-acting glucagon receptor agonist (NNC9204–0043), or both for 28 days, and a calorie-restricted weight-matched group was included to separate drug-specific from weight-dependent effects. Monotherapy with either agonist produced similar weight loss of approximately 24 %, whereas combined treatment resulted in a substantially greater reduction of 37 %. GLP-1 agonism decreased food intake, whereas glucagon agonism did not; however, glucagon agonism produced a larger reduction in hepatic triglycerides than GLP-1 agonism or weight matching, indicating hepatic effects not explained solely by weight loss. Chronic glucagon receptor activation also increased hepatic glycogen content, both alone and in combination therapy, without corresponding changes in glycogen synthase or phosphorylase activities, suggesting regulation upstream of these enzymatic pathways. These data show that combined GLP-1 and glucagon receptor agonism enhances weight loss and reduces hepatic lipid content beyond GLP-1 agonism alone. Because energy expenditure and dynamic glucose tolerance were not directly assessed, mechanistic interpretation is limited. Glucagon receptor signaling may be a key contributor to hepatic lipid metabolism and support its therapeutic potential—alone or combined with GLP-1 agonism—for improving liver health in MASLD.

胰高血糖素样肽-1 （GLP-1）和胰高血糖素受体共激动作用是治疗肥胖和代谢功能障碍相关脂肪变性肝病（MASLD）的一种新兴治疗策略。为了在反映慢性疾病的模型中检查它们的独特和联合代谢作用，我们使用了饮食诱导的肥胖小鼠，这些小鼠从成年早期开始一直保持高脂肪饮食，允许肥胖和肝脂肪变性逐渐发展并在开始治疗前保持稳定。小鼠接受长效GLP-1受体激动剂（NNC2220），长效胰高血糖素受体激动剂（NNC9204-0043），或两者兼用28天，并包括热量限制体重匹配组，以分离药物特异性和体重依赖性效应。任何一种激动剂的单药治疗产生了类似的约24%的体重减轻，而联合治疗产生了明显更大的37%的减轻。GLP-1激动剂减少食物摄入量，而胰高血糖素激动剂没有；然而，胰高血糖素激动作用比GLP-1激动作用或体重匹配作用产生更大的肝脏甘油三酯降低，表明肝脏影响不能仅仅通过体重减轻来解释。无论是单独治疗还是联合治疗，慢性胰高血糖素受体激活也增加了肝糖原含量，而糖原合成酶或磷酸化酶活性没有相应的变化，提示这些酶途径的上游调控。这些数据表明，GLP-1和胰高血糖素受体联合激动作用比单独GLP-1激动作用更能促进体重减轻，降低肝脏脂质含量。由于没有直接评估能量消耗和动态葡萄糖耐量，因此机制解释有限。胰高血糖素受体信号可能是肝脏脂质代谢的关键因素，并支持其治疗潜力-单独或与GLP-1激动剂联合-改善MASLD的肝脏健康。

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引用次数: 0

DR8 (DHNNPQIR), a rapeseed-derived peptide, mitigates fibrosis and muscle atrophy in chronic kidney disease by targeting CNR1–ERK/ELK-1 signaling DR8 （DHNNPQIR）是一种油菜籽衍生的肽，通过靶向CNR1-ERK/ELK-1信号通路减轻慢性肾脏疾病的纤维化和肌肉萎缩。

IF 2.9 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-12-01 DOI: 10.1016/j.peptides.2025.171456

Wenli Zhang , Yidan Zuo , Diyan Xu , Yibei Lin , Yaoxue Zang , Ruyi Chen , Mingli Chen , Zhen Su

DR8 (DHNNPQIR) is a rapeseed-derived bioactive octapeptide with antioxidant and anti-inflammatory properties, but its therapeutic potential in chronic kidney disease (CKD) and related muscle wasting has not been defined. In this study, we investigated the anti-fibrotic and anti-atrophic efficacy of DR8 using complementary in vitro, transcriptomic, and in vivo approaches. In TGF-β1-stimulated C2C12 myoblasts and HK-2 tubular epithelial cells, DR8 significantly attenuated fibrosis and atrophy by downregulating cannabinoid receptor 1 (CNR1) and suppressing ERK-ELK1 activation, leading to restoration of myogenic regulators (MYOD, MYOG) and inhibition of proteolytic E3 ligases (MuRF-1, MAFbx). Transcriptomic analysis identified CNR1 as a key upstream target mediating these effects. In a 5/6 nephrectomized (5/6Nx) mouse model, systemic administration of DR8 significantly improved renal function, reduced collagen accumulation, and alleviated skeletal muscle fibrosis and atrophy, accompanied by suppression of CNR1-ERK-ELK1 activation in both organs. Together, these findings demonstrate that DR8 exerts strong renoprotective and myoprotective effects through selective modulation of CNR1-dependent signaling pathways, supporting its potential as a novel peptide therapeutic for CKD-associated fibrosis and muscle wasting.

DR8 （DHNNPQIR）是一种源自油菜籽的生物活性八肽，具有抗氧化和抗炎特性，但其在慢性肾脏疾病（CKD）和相关肌肉萎缩中的治疗潜力尚未确定。在这项研究中，我们通过体外、转录组学和体内的互补方法研究了DR8的抗纤维化和抗萎缩功效。在TGF-β1刺激的C2C12成肌细胞和HK-2小管上皮细胞中，DR8通过下调大麻素受体1 （CNR1）和抑制ERK-ELK1激活，导致成肌调节因子（MYOD， MYOG）的恢复和蛋白水解E3连接酶（MuRF-1, MAFbx）的抑制，显著减轻纤维化和萎缩。转录组学分析发现CNR1是介导这些作用的关键上游靶点。在5/6肾切除（5/6Nx）小鼠模型中，全身给药DR8可显著改善肾功能，减少胶原积累，减轻骨骼肌纤维化和萎缩，同时抑制两个器官中CNR1-ERK-ELK1的激活。总之，这些发现表明DR8通过选择性调节cnr1依赖的信号通路发挥强大的肾保护和肌肉保护作用，支持其作为ckd相关纤维化和肌肉萎缩的新型肽治疗的潜力。

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引用次数: 0

Influence of the angiotensin-(1−7) on the vascular effects of the endothelin-1 in normotensive and hypertensive rats 血管紧张素-(1−7)对正常和高血压大鼠内皮素-1血管功能的影响

IF 2.9 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-12-01 DOI: 10.1016/j.peptides.2025.171455

Jaqueline Moura da Costa , Amanda de Sá Martins de Bessa , Lara Marques Naves , Monique Machado Louredo Teles , Gustavo Rodrigues Pedrino , Elizabeth Pereira Mendes , Carlos Henrique de Castro

Angiotensin-(1−7) [Ang-(1−7)] exerts cardioprotective effects through Mas receptor activation. Endothelin-1 (ET-1) is implicated in cardiovascular pathologies. Previous studies indicate a cross-talk between angiotensin and endothelin pathways; however, it remains unclear whether Ang-(1−7) differentially modulates vascular responses to ET-1 in normotensive and hypertensive conditions. This study investigated the influence of Ang-(1−7) on ET-1–induced pressor and vascular responses in normotensive and hypertensive rats (SHR). Blood pressure was recorded in conscious animals. Vascular reactivity was assessed in isolated aortic rings, and coronary effects were assessed in isolated hearts using the Langendorff technique. ET-1 increased blood pressure and reduced heart rate only in Wistar rats, effects abolished by Ang-(1−7). In normotensive rats, Ang-(1−7) potentiated ET-1–induced vasoconstriction in endothelium-intact aortas independently of Mas receptors, but had no effect in the aorta without endothelium. In hypertensive rats, Ang-(1−7) attenuated ET-1 responses in endothelium-intact aorta via Mas receptor, whereas in endothelium-denuded vessels it potentiated the vasoconstriction. In isolated hearts, ET-1 produced a biphasic response in normotensive rats (vasodilation followed by vasoconstriction) but only vasoconstriction in hypertensive rats. Ang-(1−7) potentiated vasoconstriction in normotensive but attenuated it in hypertensive hearts, which was abolished by Mas receptor blockade. These findings demonstrate that Ang-(1−7) differentially modulates ET-1 actions in normotensive and hypertensive conditions, reinforcing RAS–endothelin cross-talk. Its counter-regulatory effect in hypertension highlights Ang-(1−7) as a promising therapeutic target in cardiovascular disease.

血管紧张素-(1−7)[Ang-(1−7)]通过激活Mas受体发挥心脏保护作用。内皮素-1 （ET-1）与心血管疾病有关。先前的研究表明血管紧张素和内皮素通路之间存在交叉对话；然而，尚不清楚Ang-(1−7)是否在正常和高血压情况下调节血管对ET-1的反应。本研究探讨了Ang-(1−7)对正常和高血压大鼠（SHR） et -1诱导的升压和血管反应的影响。在有意识的动物身上记录血压。在离体主动脉环中评估血管反应性，在离体心脏中使用Langendorff技术评估冠状动脉效应。ET-1仅在Wistar大鼠中升高血压和降低心率，Ang-的作用被Ang-消除（1−7）。在血压正常的大鼠中，Ang-(1−7)增强了et -1在内皮完整的主动脉中诱导的血管收缩，而不依赖于Mas受体，但在没有内皮的主动脉中没有作用。在高血压大鼠中，Ang-(1−7)通过Mas受体减弱内皮完好主动脉中ET-1的反应，而在内皮脱落血管中，Ang-(1−7)增强血管收缩。在离体心脏中，ET-1在正常血压大鼠中产生双相反应（血管扩张后血管收缩），但在高血压大鼠中只产生血管收缩。Ang-(1−7)在血压正常的心脏中增强血管收缩，而在高血压心脏中减弱血管收缩，这一作用被Mas受体阻断所消除。这些发现表明，在正常和高血压情况下，Ang-(1−7)调节ET-1的差异作用，加强ras -内皮素的串扰。其在高血压中的反调节作用突出了Ang-(1−7)作为心血管疾病的有前途的治疗靶点。

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引用次数: 0

Greetings page 问候页面

IF 2.9 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-12-01 DOI: 10.1016/S0196-9781(25)00120-2

引用次数: 0

Reviewer Acknowledgement page 审稿人确认页

IF 2.9 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-12-01 DOI: 10.1016/S0196-9781(25)00121-4

引用次数: 0