Vascular biology (Bristol, England)最新文献

{"title":"Pharmacological and immunohistochemical characterization of dopamine D4 receptor in human umbilical artery and vein.","authors":"Pedro Renato Guazzelli, José Britto-Júnior, Pérola Rafaella Cedano Godoy P Souza, Vinicius Francisco Cardoso, Antonio Tiago Lima, Felipe Caliani Mathias Netto, Valéria Barbosa de Souza, Edson Antunes, André Schenka, Gilberto De Nucci","doi":"10.1530/VB-24-0010","DOIUrl":"10.1530/VB-24-0010","url":null,"abstract":"<p><p>To investigate the effects of the dopamine D4 receptor agonist A-412997 and the D4 antagonist sonepiprazole in human isolated umbilical artery (HUA) and vein (HUV) and the expression of the D4 receptor by immunohistochemistry in these vessels. A segment of the umbilical cord (10-20 cm) from the insertion point in the placenta and 5 cm from the umbilicus was removed by the obstetrician and placed in a container with Krebs-Henseleit solution (KHS). The Wharton's jelly was removed, and HUA and HUV rings (3 mm) were suspended in 10 mL organ baths containing oxygenated (95% O2:5% CO2) and heated (37 °C) KHS. For immunohistochemistry, the vessels were fixed in 10% formalin, embedded in paraffin wax and sectioned (4 µm). A-412997 did not induce contractions in the HUA rings. In HUA pre-contracted rings, A-412997 induced concentration-dependent relaxations, which were reduced when the HUA rings were pre-incubated with L-NAME. A-412997 caused concentration-dependent contractions of HUV rings, which were potentiated by pre-treatment with L-NAME and reduced by pre-incubation with 6-nitrodopamine. In HUV pre-contracted rings, A-412997 failed to induce relaxations. Sonepiprazole antagonized A-412997-induced contractions in HUV rings and provoked concentration-dependent relaxations in pre-contracted HUA and HUV rings. Dopamine D4 receptor was positive in both HUA and HUV, especially in the endothelium, and detected only in HUV smooth muscle cells. Activation of HUA D4 receptor is associated with relaxation, whereas in HUV, it leads to contraction. Differential expression of D4 receptors may modulate umbilical-placental blood flow.</p>","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum tissue plasminogen activator after cycling with blood flow restriction.","authors":"Josh B Landers, Melissa Allen, Ibrahim Oladele, Leah Lowe, Nawab Ali, Jacquie Rainey, James Fletcher, Korben Landers","doi":"10.1530/VB-24-0008","DOIUrl":"10.1530/VB-24-0008","url":null,"abstract":"<p><p>Blood flow restriction exercise (BFRE) is a therapeutic approach traditionally used to facilitate muscular strength and hypertrophy. Emerging evidence has identified its benefits on other systems and metabolic processes. The emphasis of this study was to examine potential impact of BFRE on serum levels of tissue plasminogen activator (tPA). Eighteen healthy adults (nine males, nine females; mean age: 34.44 ± 9.97) were randomized into groups to perform cycling either with or without blood flow restriction (BFR). Blood samples were collected before and after exercise to analyze serum concentrations of tPA. Significance in tPA between exercise groups did not reach significance but did show a large effect size (0.14) in favor of the BFR group. The trend suggests that this study was underpowered to reach significance. Further research should continue examining the impact of BFRE on serum levels of tPA. This methodology could be adapted to other populations to increase generalizability of results.</p>","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protection of liver sinusoidal endothelial cells using different preservation solutions.","authors":"Julia H E Houtzager, Anne-Marieke van Stalborch, Charlotte Hofstee, Thomas M van Gulik, Jaap D van Buul","doi":"10.1530/VB-24-0004","DOIUrl":"10.1530/VB-24-0004","url":null,"abstract":"<p><p>Donor liver preservation methods and solutions have evolved over the last years. Liver sinusoidal endothelial cell (LSEC) barrier function and integrity during preservation are crucial for outcomes of liver transplantation. Therefore, the present study aimed to determine optimal preservation of LSEC barrier function and integrity using different preservation solutions. Human umbilical vein endothelial cells (HUVECs) and LSECs were incubated in either University of Wisconsin machine perfusion solution (UW-MPS), histidine-tryptophan-ketoglutarate, or endothelial cell growth medium 2 (EGM2) (as a gold standard for cell culturing). Endothelial integrity was assessed by measurement of cellular morphology and expression of membrane proteins: PECAM-1, ICAM-1 and Fc-gamma receptor CD32b (FcΥRCD32b). Endothelial barrier function was measured by electric cell-substrate impedance sensing. Cellular response to inflammatory stimuli with tumor necrosis factor-alpha (TNF-α) was tested by studying trans-endothelial migration (TEM) under flow conditions. Differences in these parameters were analyzed between the different preservation solutions. PECAM-1 expression was high for all preservation solutions in HUVECs and LSECs. ICAM-1 expression was increased in both LSECs and HUVECs in all preservation solutions plus TNF-α. UW reduced PECAM-1 expression, whereas EGM2 medium promoted barrier function in LSECs and HUVECs, and monolayer recovery after wounding was best achieved in cells incubated in EGM2. LSECs and HUVECs incubated with EGM2 plus TNF-α both supported neutrophil adhesion and TEM, but much less to none when incubated in UW plus TNF-α. Overall, EGM2 showed the best results in preserving endothelial barrier function for both HUVECs and LSECs.</p>","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lack of intracranial atherosclerosis in various atherosclerotic mouse models.","authors":"Diewertje I Bink, Katja Ritz, Claire Mackaaij, Olga Stam, Sanny Scheffer, Mark R Mizee, Hanneke J Ploegmakers, Bert J van Het Hof, Onno J de Boer, Judith C Sluimer, Guido R Y De Meyer, Louise van der Weerd, Helga E de Vries, Mat J A P Daemen","doi":"10.1530/VB-23-0013","DOIUrl":"10.1530/VB-23-0013","url":null,"abstract":"<p><p>Although mice are used extensively to study atherosclerosis of different vascular beds, limited data are published on the occurrence of intracranial atherosclerosis. Since intracranial atherosclerosis is a common cause of stroke and is associated with dementia, a relevant animal model is needed to study these diseases. We examined the presence of intracranial atherosclerosis in different atherogenic mouse strains and studied differences in vessel wall characteristics in mouse and human tissue in search of possible explanations for the differing atherosclerotic susceptibility between extracranial and intracranial vessels. The presence of atherosclerotic plaques was systematically examined from the distal common carotids to the circle of Willis in three atherogenic mouse models. Extra- and intracranial vessel characteristics were studied by immunohistochemistry. All three strains developed atherosclerotic lesions in the common carotids, while no lesions were found intracranially. This coincided with altered vessel morphology. Compared to extracranial sections, intracranially the number of elastic layers decreased, tight junction markers increased, and antioxidant enzyme heme oxygenase (HO)-1 increased. Higher HO-1 expression was also shown in human intracranial arteries. Human brain endothelial cell stimulation with oxidized LDL induced endogenous protective antioxidant HO-1 levels through NRF2 translocation. Intracranial atherosclerosis was absent in three atherogenic mouse models. Intracranial vessel segments showed an increased presence of junction markers in mice and increased HO-1 in both mice and human tissue. We suggest that differences in brain vessel structure and induced antioxidant levels in the brain endothelium found in mouse and human tissue may contribute to the decreased atherosclerosis susceptibility of intracranial arteries.</p>","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic angiogenesis for patients with chronic limb-threatening ischemia: promising or hoax?","authors":"Judith A H M Peeters, Abbey Schepers, Jaap F Hamming, Paul H A Quax","doi":"10.1530/VB-24-0009","DOIUrl":"10.1530/VB-24-0009","url":null,"abstract":"<p><p>Chronic limb-threatening ischemia (CLTI) is a critical end-stage disease that leads to high amputation rates. Over the past few decades, therapeutic angiogenesis has attracted a lot of attention as a means to reduce the necessity for amputations. Especially gene- and cell therapy are regarded to as possible treatment modalities to restore the hampered blood flow. So far, early-phase clinical trials often fail to prove a significant clinical improvement in mortality, amputation rate, and ulcer healing but still conclude that therapeutic angiogenesis might be promising as therapy. The subsequent phase III clinical trials based on these indecisive early trials fail consistently to demonstrate clinical benefits leaving the promising early results unvalidated. In this review we will illustrate that designing good trials for CLTI patients is challenging, not in the last place since patients are often not eligible due to strict inclusion criteria. Moreover, in this review, we advocate that clinical trials should be conducted with a low risk of bias and that it is of utmost importance to publish results, regardless of the outcome. It is definitely very concerning that many studies of a lower quality (due to small group size or high chance for bias) reporting positive outcomes are published while good quality trials (often with larger group sizes) are stopped prematurely due to lack of effects and remain unpublished. This keeps the 'promising but not yet proven' image of these therapeutic neovascularization studies alive, with still new groups starting similar trials.</p>","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole-body insulin resistance leads to accelerated atherosclerosis: role for Nox2 NADPH oxidase.","authors":"Azhar Maqbool, Hema Viswambharan, Anna Skromna, Natallia Makava, Heba Shawer, Katherine Bridge, Shovkat Kadirovich Muminov, Helen Imrie, Kathryn Griffin, Stephen B Wheatcroft, Piruthivi Sukumar, Richard M Cubbon, Mark T Kearney, Nadira Yusupovna Yuldasheva","doi":"10.1530/VB-23-0018","DOIUrl":"10.1530/VB-23-0018","url":null,"abstract":"<p><p>Insulin resistance underpins the progression of type 2 diabetes mellitus and leads to a collection of risk factors for the development of atherosclerosis. Whether or not insulin resistance at a whole-body level per se leads to accelerated atherosclerosis is unclear. To answer this question, we generated atherosclerosis-prone mice with whole-body insulin resistance secondary to haploinsufficiency of the insulin receptor (IR+/-) deficient in ApoE-/- (IR+/-/ApoE-/-). IR+/-/ApoE-/- and ApoE-/- littermates had similar weight, lipids, and glucose tolerance at baseline. After 12 weeks of Western high-cholesterol diet, IR+/-/ApoE-/- had significantly more atherosclerosis in the thoracoabdominal aorta and at the level of the aortic sinus than ApoE-/- littermates. Excess Nox2 NADPH oxidase (Nox2) derived superoxide has been suggested to underpin diabetes-related atherosclerosis. In IR+/-/ApoE-/- we examined the effect of inhibiting Nox2 using genetic or pharmacological approaches on the development of atherosclerosis. To genetically delete Nox2, we generated IR+/-/ApoE-/-/Nox2-/y and to inhibit Nox2 pharmacologically, we treated IR+/-/ApoE-/- with the peptide Nox2 inhibitor gp91dstat. IR+/-/ApoE-/-/Nox2-/y had significant disruption of the aortic wall with increased thoracoabdominal atherosclerosis when compared to IR+/-/ApoE-/-/Nox2+/y littermates. Inhibition of Nox2 using gp91dstat reduced atherosclerosis in the thoracoabdominal aorta of IR+/-/ApoE-/-. Whole-body insulin resistance accelerates the development of atherosclerosis. Genetic inhibition of Nox2 leads to disruption of the aortic wall in IR+/-/ApoE-/- mice with accelerated atherosclerosis, whereas pharmacological Nox2 inhibition reduces atherosclerosis in IR+/-/ApoE-/- without disruption of the arterial wall.</p>","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ang II-induced contraction is impaired in the aortas of renovascular hypertensive animal model.","authors":"Bernah M Fahning, Simone R Potje, Tiago D Paula, Marcella D Grando, Lusiane M Bendhack","doi":"10.1530/VB-23-0021","DOIUrl":"10.1530/VB-23-0021","url":null,"abstract":"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong>Renin-angiotensin system plays a critical role in blood pressure control, and the abnormal activation of the AT1 receptor contributes to the development of renovascular hypertension. This study aimed to evaluate the underlying cellular signaling for AT1 receptor activation by Ang II and to compare this mechanism between aortas from 2K-1C and 2K rats. Effects of antagonists and inhibitors were investigated on Ang II-induced contractions in denuded or intact-endothelium aortas. The AT1 receptor antagonist abolished Ang II-induced contraction in 2K-1C and 2K rat aortas, while AT2 and Mas receptors antagonists had no effect. Endothelial nitric oxide synthase inhibition increased the maximal effect (Emax) of Ang II in 2K, which was not changed in 2K-1C aortas. It was associated with lower eNOS mRNA levels in 2K-1C. Endothelium removal increased the Emax of Ang II in 2K-1C and mainly in 2K rat aortas. Nox and COX inhibition did not alter Ang II-induced contraction in 2K and 2K-1C rat aortas. However, AT1 expression was higher in 2K-1C compared to 2K rat aortic rings, whereas expression of phosphorylated (active) IP3 receptors was lower in 2K-1C than in 2K rats. These results demonstrate that endothelium removal impairs Ang II-stimulated contraction in the aorta of 2K-1C rats, which is associated with the reduction of IP3 receptor phosphorylation and activation. In addition, eNOS plays a critical role in Ang II-induced contraction in 2K rat aortas. It is possible that the high Ang II plasma levels could desensitize AT1 receptor in 2K-1C rats, leading to impaired IP3 receptors activation.</p>","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11227066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141285554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPX4 overexpression does not alter atherosclerotic plaque development in ApoE knock-out mice.","authors":"Isabelle Coornaert, Annelies Breynaert, Nina Hermans, Guido R Y De Meyer, Wim Martinet","doi":"10.1530/VB-23-0020","DOIUrl":"10.1530/VB-23-0020","url":null,"abstract":"<p><p>Ferroptosis is a type of regulated necrosis that is associated with iron-dependent accumulation of lipid hydroperoxides. Given that iron deposition and lipid peroxidation initiate ferroptosis in atherosclerosis and contribute to further plaque development, we hypothesized that inhibition of ferroptosis could be of value in the treatment of atherosclerosis. Glutathione peroxidase 4 (GPX4) is the only enzyme known capable of reducing lipid hydroperoxides. Previous studies have demonstrated that inactivation of GPX4 results in ferroptosis, while overexpression of GPX4 confers resistance to ferroptosis. In the present study, we examined the impact of GPX4 overexpression on the development of atherosclerotic plaques. GPX4-overexpressing mice (GPX4Tg/+) were crossbred with ApoE-/- mice and fed a western-type diet for 16 weeks. Atherosclerotic plaques of GPX4Tg/+ ApoE-/- mice showed increased GPX4 expression and a reduced amount of lipid hydroperoxides. However, plaque size and composition were not different as compared to control animals. Similarly, GPX4-overexpressing vascular smooth muscle cells and bone marrow-derived macrophages were not protected against lipid peroxidation and cell death triggered by the ferroptosis inducers erastin and 1S,3R-RSL3. We concluded that GPX4 overexpression reduces lipid peroxidation in plaques of ApoE-/- mice, yet GPX4 overexpression is not sufficiently powerful to change plaque size or composition.</p>","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11227057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"α-Tocopherol inhibits atherogenesis and improves cardiac function in mice independently of its antioxidant properties.","authors":"Isabelle Coornaert, Annelies Breynaert, Nina Hermans, Guido R Y De Meyer, Wim Martinet","doi":"10.1530/VB-24-0002","DOIUrl":"10.1530/VB-24-0002","url":null,"abstract":"<p><p>The impact of α-tocopherol on atherosclerosis is unclear and controversial. While some studies suggest potential benefits, such as antioxidant properties that may reduce oxidative stress, other studies indicate no significant preventive effects. The intricate interplay of various factors, including dosage, individual differences, and study methodologies, contributes to the ongoing uncertainty surrounding α-tocopherol's role in atherosclerosis. Further research is needed to clarify its impact and establish clearer guidelines. Therefore, we aimed to evaluate the impact of α-tocopherol on atherogenesis in ApoE-/- fibrillin (Fbn)1C1039G/+ mice, which is a unique mouse model of advanced atherosclerosis with typical features, such as large necrotic cores, high levels of inflammation, and intraplaque neovascularization, that resemble the unstable phenotype of human plaques. ApoE-/- Fbn1C1039G+/- mice were fed a western-type diet (WD) supplemented with a high dose of α-tocopherol (500 mg/kg diet), while control mice were fed a WD containing a low dose of α-tocopherol (50 mg/kg diet). The high dose of α-tocopherol reduced plaque thickness and necrotic core area in the right common carotid artery (RCCA) after 24 weeks WD. Moreover, α-tocopherol decreased plaque formation and intraplaque neovascularization in the RCCA. In addition to its antiatherogenic effect, chronic supplementation of α-tocopherol improved cardiac function in ApoE-/- Fbn1C1039G/+ mice. However, chronic supplementation of α-tocopherol did not decrease lipid peroxidation. On the contrary, α-tocopherol acted as a prooxidant by increasing plasma levels of oxidized LDL and plaque malondialdehyde, an end product of lipid peroxidation. Our data indicate that α-tocopherol inhibits atherogenesis and improves cardiac function independent of its antioxidant properties.</p>","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11227056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atherosclerosis: an overview of mouse models and a detailed methodology to quantify lesions in the aortic root.","authors":"Jamie I van der Vaart, Robin van Eenige, Patrick C N Rensen, Sander Kooijman","doi":"10.1530/VB-23-0017","DOIUrl":"10.1530/VB-23-0017","url":null,"abstract":"<p><p>Cardiovascular disease, the primary cause of human mortality globally, is predominantly caused by a progressive disorder known as atherosclerosis. Atherosclerosis refers to the process of accumulation of cholesterol-enriched lipoproteins and the concomitant initiation of inflammatory processes in the arterial wall, including the recruitment of immune cells. This leads to the formation of atherosclerotic plaques, initially causing a thickening of the arterial wall and narrowing of arteries. However, as plaque formation progresses, atherosclerotic plaques may become unstable and rupture, leading to a blood clot that blocks the affected artery or travels through the blood to block blood flow elsewhere. In the early 1990s, emerging gene editing methods enabled the development of apolipoprotein E knockout (Apoe-/- ) and low-density lipoprotein receptor knockout (Ldlr-/- ) mice. These mice have been instrumental in unraveling the complex pathogenesis of atherosclerosis. Around the same time, human APOE*3-Leiden transgenic mice were generated, which were more recently cross-bred with human cholesteryl ester transfer protein (CETP) transgenic mice to generate APOE*3-Leiden.CETP mice. This model appears to closely mimic human lipoprotein metabolism and responds to classic lipid-lowering interventions due to an intact ApoE-LDLR pathway of lipoprotein remnant clearance. In this review, we describe the role of lipid metabolism and inflammation in atherosclerosis development and highlight the characteristics of the frequently used animal models to study atherosclerosis, with a focus on mouse models, discussing their advantages and limitations. Moreover, we present a detailed methodology to quantify atherosclerotic lesion area within the aortic root region of the murine heart, as well as details required for scoring atherosclerotic lesion severity based on guidelines of the American Heart Association adapted for mice.</p>","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11046329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}