Clinical science最新文献

{"title":"Epac1 mediates thermogenesis and lipolysis in white adipose tissue via p38γ-NFAT5 axis in a PKA-independent manner.","authors":"Baile Wang, Christina Chen, Jie Liu, Qin Wang, Wenxia Zhang, Jingwen Liu, Andrew Tai, Alan Kai, Ben Ko, Aimin Xu, Sookja Chung","doi":"10.1042/CS20256710","DOIUrl":"https://doi.org/10.1042/CS20256710","url":null,"abstract":"<p><p>Beige adipocytes in white adipose tissue (WAT) shares similar functions as brown adipocytes by converting lipids into heat through thermogenesis, while lipolysis is considered as a prerequisite for the activation of non-shivering thermogenesis. β3-adrenergic receptor (β3-AR) agonist CL316,243 (CL) and cold exposure are known to enhance lipolysis and beiging of WAT in a PKA-dependent manner, while the role of PKA-independent pathways involved are still poorly understood. Here, we show that the exchange protein directly activated by cAMP 1 (Epac1), a downstream target of cAMP, mediates β3-AR activation to modulate thermogenesis and lipolysis in a PKA-independent manner. Upon CL treatment or cold exposure, both thermogenic and lipolytic responses were compromised in Epac1-deficient mice, as evidenced by reduced oxygen consumption, less beige adipocytes, lower body temperature, and decreased circulating glycerol. Additionally, in vitro beige adipogenesis with or without cAMP analog treatment was significantly impaired in Epac1-deficient mice. Mechanistically, reduced total and phosphorylated p38γ and decreased induction of nuclear factor activated in T cells 5 (NFAT5) were observed in Epac1-deficient mice, which may contribute to the defective beiging of WAT. However, WAT of wild-type and Epac1-deficient mice showed no significant induction difference in phosphorylation of HSL at PKA and AMPK sites with PKA activator, and in vitro beige adipogenesis was not altered in Epac1-deficient mice in response to PKA activation, indicating that Epac1 mediates lipolysis and beige adipogenesis in a PKA-independent manner. Taken together, Epac1 mediates β3-AR induced beiging and lipolysis of WAT via p38γ-NFAT5 axis in a PKA-independent manner.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reductions in angiotensin II type 2 receptor-mediated vasodilation contribute to increased angiotensin II vasoconstrictor sensitivity in women with preeclampsia history.","authors":"Kelsey Schwartz, Nathan Campbell, Diana Jalal, Anna Stanhewicz","doi":"10.1042/CS20245238","DOIUrl":"https://doi.org/10.1042/CS20245238","url":null,"abstract":"<p><p>Women with a history of preeclampsia (hxPE) have a ≥4-fold risk for developing cardiovascular disease (CVD) compared with women who had a healthy pregnancy (hxHC). HxPE have exaggerated vasoconstrictor sensitivity to angiotensin (ang) II after pregnancy, which likely contributes to CVD progression after preeclampsia. Ang II-mediated constriction via ang II type 1 receptors (AT1R) is countered by vasodilatory ang II type 2 receptors (AT2R); however, the extent that reductions in AT2R-mediated responses contribute to exaggerated ang II-mediated constriction after preeclampsia is unknown. We examined the balance of AT1R- and AT2R-mediated responses in hxPE and hxHC (n=12/group). We hypothesized that 1) attenuated AT2R-mediated dilation would be improved with AT1R inhibition in hxPE, and 2) AT2R inhibition would increase ang II-mediated constriction in hxHC but have no effect in hxPE. We measured cutaneous vascular conductance responses to compound 21 (AT2R agonist; 10-14-10-8mol/L) alone or with losartan (AT1R antagonist; 43µmol/L) to assess AT2R-mediated dilation, and ang II (10-20-10-4mol/L) alone or with PD-123319 (AT2R antagonist; 1µmol/L) to assess the role of AT2R in vasoconstrictor sensitivity to ang II. Reduced AT2R-mediated dilation in hxPE (P=0.002) was improved with AT1R inhibition (P<0.001). Vasoconstrictor sensitivity to ang II was greater in hxPE compared with hxHC (P<0.001). Circulating AT1R agonistic autoantibodies (AT1-AA) were elevated in hxPE (P=0.015). AT2R inhibition increased the vasoconstrictor response to ang II in hxHC (P<0.001) but had no effect in hxPE (P=0.19). These data suggest that hxPE have reduced AT2R-mediated dilation that contributes to increased ang II vasoconstrictor sensitivity after preeclampsia.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering complexity of GPCR signaling and modulation: implications and perspectives for drug discovery.","authors":"Claudio M Costa-Neto, Lucas T Parreiras-E-Silva","doi":"10.1042/CS20245182","DOIUrl":"https://doi.org/10.1042/CS20245182","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) are central to pathophysiological processes and remain prominent targets in drug discovery. Recent advances in understanding GPCR signaling and modulation, such as biased agonism, dual agonism, and non-canonical G protein signaling, have expanded the therapeutic landscape of these receptors. These understandings have led (and are leading further) to innovative approaches that broaden GPCRs as therapeutic targets, going after better efficacy and minimizing adverse effects. However, tachyphylaxis, a rapid decrease in receptor responsiveness after repeated stimulation, presents a significant challenge in a chronic treatment context. Recent findings from our group revealed that tachyphylaxis in the angiotensin type 1 (AT1) receptor is primarily governed by the ligand's dissociation rate (koff), i.e. high residence time, rather than by β-arrestin-mediated desensitization, as could be expected. This suggests that internalized AT1 receptors remain active when bound to ligands with high residence time, favoring sustained signaling from endosomes. Importantly, the concept of high residence time sheds new light on intracellular signaling phenomena and underscores the therapeutic value of modulating intracellular receptor activity, including the development of novel cell-permeant antagonists. This review discusses critical pharmacological parameters for drug discovery focused on agonists, including (i) activation of preferential signaling pathways (biased agonism), (ii) internalization/recycling rates, (iii) tachyphylaxis/desensitization, (iv) allosteric modulators, and (v) intracellular receptor signaling and its blockade, emphasizing the need for strategies that extend beyond conventional GPCRs' functional assays. Additionally, this review highlights how advancements in high-resolution imaging, bioluminescence resonance energy transfer-based biosensors, and computational modeling are crucial for elucidating complex GPCRs' behaviors, particularly in understanding mechanisms like tachyphylaxis and its interplay with compartment-specific signaling. These approaches not only pave the way for therapies that strategically leverage or mitigate tachyphylaxis to sustain receptor responsiveness, but could enable the design of drugs targeting intracellular pathways as a strategy to enhance efficacy and minimize adverse effects. These insights underscore the importance of integrating diverse pharmacological strategies to refine GPCR-targeted therapies and address unmet medical needs, particularly in chronic conditions where sustained receptor activity is critical.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"139 10","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LONP1 facilitates pulmonary artery smooth muscle cell glycolytic reprogramming by degrading MPC1 in pulmonary hypertension.","authors":"Mingkang Li, Wenkang Zhang, Minhao Zhang, Linqing Li, Yuyu Yao, Yuhan Qin, Dong Wang, Gaoliang Yan, Yong Qiao, Chengchun Tang","doi":"10.1042/CS20255922","DOIUrl":"10.1042/CS20255922","url":null,"abstract":"<p><p>Pulmonary hypertension (PH) is a chronic and life-threatening disease characterized by pulmonary vascular remodeling (PVR), which involves the abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs). These cells exhibit metabolic characteristics akin to cancer cells, particularly in their shift toward glycolysis. The Lon protease 1 (LONP1) has been shown to promote glycolytic reprogramming of tumor cells, conferring a malignant proliferative phenotype. However, the precise role of LONP1 in PH remains unclear. In the present study, Su5416/hypoxia-induced and monocrotaline (MCT)-induced PH rodent models and platelet-derived growth factor BB (PDGF-BB)-induced PASMCs were used to investigate the role and mechanism of LONP1 in PH. The results revealed an up-regulation of LONP1 expression in lung tissues from two PH rodent models, as well as in PDGF-BB-induced PASMCs. In vivo knockdown of LONP1 significantly alleviated PASMC mitochondrial dysfunction, reduced glycolytic enzyme expression, and decreased lactate accumulation, thereby mitigating PVR. Additionally, in vitro experiments demonstrated that knockdown or inhibition of LONP1 attenuated glycolytic reprogramming, proliferation, and migration of PASMCs, whereas overexpression of LONP1 had converse effects. Mechanistic studies confirmed that mitochondrial pyruvate carrier 1 (MPC1) was a direct substrate for LONP1-mediated degradation. Functional experiments with MPC1 knockdown and overexpression further elucidated its role in the proliferation and migration of PASMCs. Rescue experiments indicated that MPC1 knockdown abrogated the suppressive effects of LONP1 knockdown on glycolytic reprogramming, proliferation, and migration in PASMCs. Therapeutically, knockdown or pharmacological inhibition of LONP1 significantly reversed MCT-induced PH in rats. Thus, targeting LONP1 may represent a promising therapeutic strategy for PH.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased absorptive transcytosis and tight junction weakness in heart failure are equally corrected by exercise training and losartan.","authors":"Hiviny de Ataides Raquel, Mariana Makuch-Martins, Sany M Perego, Gustavo S Masson, Leonardo Jensen, Lisete C Michelini","doi":"10.1042/CS20242965","DOIUrl":"https://doi.org/10.1042/CS20242965","url":null,"abstract":"<p><p>Reduced ventricular function, renin-angiotensin system upregulation and sympathoexcitation are hallmarks of heart failure (HF). Recently we showed that blood-brain barrier (BBB) lesion within autonomic nuclei contributes to autonomic imbalance and that exercise training (T) normalizes BBB function and improves autonomic control. We sought now to identify the mechanism( involved in both HF-induced lesion and exercise-induced correction. Wistar rats submitted to coronary artery ligation were, after the development of HF, assigned to losartan (Los) or vehicle (Veh) treatments and simultaneously submitted to T or sedentary ( protocol. After hemodynamic/autonomic recordings and evaluation of BBB permeability, brains were harvested for ultrastructural analyses of the barrier (tight junctions (TJ) tightness and vesicles trafficking) within capillaries of the hypothalamic paraventricular nucleus. Local angiotensin II (Ang II) expression and activation of microglial cells (IBA-1 immunofluorescence) were also evaluated. High sympathetic activity and pressure variability, reduced parasympathetic control of the heart, elevated BBB permeability, high vesicular trafficking and TJ weakness exhibited by Veh-rats were equally corrected in Veh-T, Los-and Los-T groups. The increased PVN Ang II expression and IBA-1 density in Veh-group were similarly reduced by T, Los and combination of both. Ang II, colocalized with microglia AT1 receptors, induced their remodeling from disease-associated phenotype in Veh-S rats to homeostatic-surveilling conditions in the other groups. All measured parameters exhibited strong correlations with Ang II availability. Data indicated that changes in PVN Ang II availability induced by HF, exercise and losartan is the key regulator of transcellular and paracellular transport across the BBB.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Physiological response to fetal intravenous lipid emulsion.","authors":"","doi":"10.1042/CS20231419_COR","DOIUrl":"https://doi.org/10.1042/CS20231419_COR","url":null,"abstract":"","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"139 10","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum proteomics links the cardiorespiratory biomarkers CTRC, OSM, and MMP-10 to exacerbation severity and number in patients with COPD.","authors":"Eduardo I Cardenas, Kristina Andelid, Nikolaos Pournaras, Ann Ekberg- Jansson, Nicola Orsini, Georgios Stratelis, Tomas Jernberg, Anders Lindén","doi":"10.1042/CS20255852","DOIUrl":"https://doi.org/10.1042/CS20255852","url":null,"abstract":"<p><p>During exacerbations, patients with chronic obstructive pulmonary disease (COPD) are at risk for severe cardiovascular disease (CVD). Despite this, the available literature on systemic biomarkers of CVD during exacerbations is limited. In the present study, a proteomic approach was used to assess alterations in the concentrations of 177 biomarkers of CVD and inflammation in serum samples from 26 long-term smokers (LTS) with mild-to-severe COPD (GOLD stage 1-3) and chronic bronchitis (COPD-CB) but no allergy. These patients were followed for 60 weeks, and they all provided paired samples during stable disease and exacerbations. Serum samples from ten healthy non-smokers (HNS) and ten LTS without COPD or CB constituted controls. Of all the proteins analyzed, only chymotrypsin C (CTRC), oncostatin M (OSM), and matrix metalloproteinase 10 (MMP-10) displayed significantly altered concentrations during exacerbations in the COPD-CB group. Here, the concentrations of CTRC and OSM correlated with exacerbation severity, CRP, blood leukocytes, and other cardiovascular biomarkers. In contrast, the concentration of MMP-10 during stable disease correlated with blood eosinophil counts and exacerbation numbers. Finally, the concentrations of OSM and MMP-10 during stable disease correlated with blood leukocytes and tobacco load, respectively. Our study suggests that CTRC, OSM, and MMP-10 bear potential as cardiorespiratory biomarkers in patients with COPD and CB. Collectively, these biomarkers display substantial alterations during exacerbations and correlate with the severity and number of exacerbations. These results motivate prospective studies to determine the clinical utility of CTRC, OSM, and MMP-10 in assessing cardiorespiratory risk in patients with COPD.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"139 9","pages":"449-462"},"PeriodicalIF":6.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-talk between microbiota-gut-brain axis and blood pressure regulation.","authors":"Malindi Welathanthree, Damien J Keating, Vaughan G Macefield, Daniela Carnevale, Francine Z Marques, Rikeish R Muralitharan","doi":"10.1042/CS20240787","DOIUrl":"https://doi.org/10.1042/CS20240787","url":null,"abstract":"<p><p>Hypertension, or high blood pressure (BP), is a widespread condition affecting one in three adults globally. Despite the availability of treatment options, 50% of hypertensive patients in countries such as Australia fail to achieve adequate BP control, often due to a lack of response to current therapies. Diet plays a crucial role in BP regulation. A high-fibre diet reduces BP through the gut microbiome and the production of microbial metabolites known as short-chain fatty acids (SCFAs). However, the mechanisms of BP regulation by SCFAs remained still unclear. A novel hypothesis we explore in this review is that these microbial metabolites may regulate BP via the activation of central mechanisms, a phenomenon called the gut-brain axis. While substantial evidence in animal models and humans supports the protective role of SCFAs in hypertension, the precise mechanisms remain unclear. SCFA stimulates the release of neurotransmitters and hormones such as serotonin, cholecystokinin, glucagon-like peptide 1 and peptide YY by enteroendocrine cells, a rare population of cells lining the gastrointestinal tract. These hormones bind to their receptors on the peripheral nervous system nerves, such as the vagus and spinal nerves, conveying information to the brain. The mechanisms by which information is relayed from the gut microbiome to the brain likely involve the immune system and gut-derived neurotransmitters and hormones. A deeper understanding of these pathways and mechanisms will facilitate the development of novel therapeutics for hypertension and other cardiovascular diseases.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"139 9","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of metformin in a novel experimental model of peripheral artery disease.","authors":"Smriti Krishna, Joseph V Moxon, Ann-Katrin Kraeuter, Jonathan Golledge","doi":"10.1042/CS20243343","DOIUrl":"https://doi.org/10.1042/CS20243343","url":null,"abstract":"<p><p>Limited drug therapies for peripheral artery disease (PAD)-related walking impairment exist. There has been recent in repurposing the diabetes medication metformin to treat PAD. Animal studies designed to develop new PAD drug therapies have mainly used a model of temporary hind limb ischemia (HLI). The aim of this study was to test whether metformin improved blood supply and ambulation in a novel mouse model with ongoing HLI. Stable HLI was created in apolipoprotein E deficient mice by a two-stage surgical procedure. Five days after HLI was induced, mice were randomly allocated to receive metformin (n=16; 300mg/kg/day) or vehicle control (n=15) by oral gavage for four weeks. The primary outcome was hind limb blood supply assessed by laser Doppler. Other outcomes included treadmill performance and molecular changes in the ischemic limb. Metformin improved hind limb blood supply (p<0.001), but not physical performance, associated with increased phosphorylation of 5' adenosine monophosphate-activated protein kinase and endothelial nitric oxide synthase (p<0.05), reduced expression of thioredoxin interacting protein (p<0.05) and increased expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (p<0.05) in the ischemic muscles and increased circulating nitric oxide levels (p<0.05). Metformin improved blood supply in a novel model of limb ischemia associated with molecular changes previously linked with promoting angiogenesis but these changes did not translate to improved physical performance. The findings suggest that laser Doppler hind limb blood supply may not be an ideal outcome measure to gauge the success of a drug in patients with PAD-related walking impairment.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nicotine promotes AngII-induced abdominal aortic aortopathies in female and male mice: role of sex hormones.","authors":"Mark Ensor, Sean E Thatcher, Kristen McQuerry, Kory Heier, Heba M Ali, Victoria English, Lisa A Cassis, Yasir Alsiraj","doi":"10.1042/CS20255689","DOIUrl":"10.1042/CS20255689","url":null,"abstract":"<p><p>Cigarette smoking is a risk factor for abdominal aortic aneurysms (AAAs), with studies suggesting a higher smoking-related AAA risk in women than men. We examined nicotine's effects on angiotensin II (AngII)-induced AAAs in male and female low-density lipoprotein receptor-deficient (Ldlr-/-) mice. Moreover, we defined effects of gonadectomy (GDX) of both sexes on nicotine-induced regulation of AAAs. Male and female Ldlr-/- mice (8-12 weeks of age) were infused with AngII with or without nicotine. Mice underwent sham or GDX surgeries prior to infusions of AngII and nicotine. In males, one or both testes were removed. AAA incidence, size, severity, and serum indices of nicotine metabolism were quantified. Effects of testosterone or estrogen on abdominal aortic smooth muscle cells (SMCs) were assessed. Nicotine increased aortic rupture in males, with modest effects in females. GDX reduced AAA incidence in male mice but had modest effects in females. Serum ratios of trans-3-hydroxycotinine to cotinine, an index of nicotine metabolism, were higher in females and increased by GDX in both sexes. Co-infusion of nicotine with AngII increased matrix metalloproteinase 2 (MMP2) mRNA in abdominal aortas of males, but not females. Similarly, testosterone increased MMP2 mRNA in male, but not female abdominal aortic SMCs. Testosterone reduced markers of a contractile SMC phenotype in SMCs from males, with no effects of estrogen in females. In conclusion, nicotine augments AngII-induced AAAs to a greater extent in males, with sex differences related to influences of sex hormones on nicotine metabolism, aortic MMP2 expression, and markers of a contractile SMC phenotype.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}