Puerarin protects against endothelial dysfunction and end-organ damage in Ang II-induced hypertension

Previously we have shown that Group IV cytosolic phospholipase A 2 α (cPLA 2 α) is critical for the development of angiotensin (Ang) II-induced hypertension, cardiovascular dysfunction and fibrosis. This study was conducted to determine the role of cPLA 2 α in renal dysfunction and end organ damage associated with Ang II-induced hypertension. Eight weeks old male wild type (cPLA 2 α +/+ ) and cPLA 2 α knockout (cPLA 2 α -/- ) mice were infused with Ang II (700 ng/kg/min) or its vehicle for 2 weeks and systolic blood pressure (SBP) was measured weekly by the tail cuff method. Ang II increased SBP (mmHg) in cPLA 2 α +/+ mice to a greater degree than in cPLA 2 α -/- mice (125 ± 2 to 186 ± 7 vs. 125 ± 2 to 132 ± 2 respectively, P< 0.05). Ang II caused renal fibrosis as indicated by accumulation of α-smooth muscle actin, transforming growth factor-β-positive cells and collagen deposition in the kidneys of cPLA 2 α +/+ but not cPLA 2 α -/- mice. Ang II infusion increased reactive oxygen species production in the kidney measured by 2-hydroxyethidium fluorescence (AU), in cPLA 2 α +/+ mice (16.14 ± 0.61 vehicle vs. 24.08 ± 0.61 Ang II P < 0.05) but not in cPLA 2 α -/- mice (16.93 ± 0.58 vehicle vs. 17.19 ± 0.93 Ang II). Mice were placed in metabolic cages to monitor their water intake and urine output. After 13 days of Ang II infusion, 24 hr water intake was increased (4.33 ± 0.14 ml to 8.17 ± 0.27 ml P < 0.05) in cPLA 2 α +/+ mice but not in cPLA 2 α -/- mice (4.87 ± 0.22 ml to 4.8 ± 0.27 ml). Twenty-four hr urine output (μl) was increased to a greater extent in cPLA 2 α +/+ mice (423.33 ± 67.26 to 2030.94 ± 191.58 P < 0.05) vs. cPLA 2 α -/- mice (374.37 ± 66.89 to 787.37 ± 126.50). Urine osmolality (mOsm/kg) was decreased (3778.33 ± 240.21 to 1620 ± 129.23 P < 0.05) in cPLA 2 α +/+ but not in cPLA 2 α -/- mice (4042 ± 306.07 to 3372.5 ± 43.27), and proteinuria (mg/24hr) increased to a greater extent in cPLA 2 α +/+ mice (2.07 ± 0.11 to 6.99 ± 0.34 P < 0.05) vs. cPLA 2 α -/- mice (1.95 ± 0.07 to 3.03 ± 0.20 in cPLA 2 α -/- ). These data suggest that cPLA 2 α contributes to Ang II-induced hypertension, associated renal dysfunction and end organ damage, most likely due to release of arachidonic acid, activation of NADPH oxidase and generation of ROS. Thus, cPLA 2 α could serve as a potential therapeutic target in the treatment of hypertension and end organ damage.

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Abstract P135: 2-methoxyestradiol Minimizes Angiotensin II-induced Hypertension and Renal Dysfunction in Ovariectomized Female and Intact Male Mice

Hypertension ◽

10.1161/hyp.68.suppl_1.p135 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Ajeeth K Pingili ◽

Shyamala Thirunavukkarasu ◽

Nayaab S Khan ◽

Akemi Katsurada ◽

Dewan S Majid ◽

...

Keyword(s):

Angiotensin Ii ◽

Renal Dysfunction ◽

Organ Damage ◽

Ang Ii ◽

Male Mice ◽

Intact Male ◽

Female Mice ◽

End Organ Damage ◽

Induced Hypertension ◽

Post Menopausal

Men and post-menopausal females are more prone to develop hypertension and renal dysfunction as compared to pre-menopausal females. It is well documented that in various experimental models of hypertension, the protection against hypertension in females is lost following ovariectomy (OVX). Recently we have shown that CYP1B1 protects against angiotensin II (Ang II)-induced hypertension and associated cardiovascular changes in female mice, most likely via production of 2-methoxyestradiol (2-ME). This study was conducted to determine if 2-ME reduces Ang II-induced hypertension, renal dysfunction and end organ damage in OVX female, and intact male mice. Treatment of OVX Cyp1b1 +/+ and Cyp1b1 -/- female mice with 2-ME (1.5 mg/kg/day i.p., for 2 weeks) reduced Ang II-induced increase in systolic blood pressure (SBP) (182±5.1 vs. 143± 2.4 mmHg, 179±6.4 vs. 140± 8.6 mmHg, P < 0.05, n= 5), water consumption, urine output and osmolality, and proteinuria (5.5±0.7 vs. 3.3±0.5 mg/24 hrs, 8.4±1.3 vs. 4.4 ±0.9 mg/24 hrs) respectively. 2-ME also reduced Ang II-induced increase in SBP (188±2.6 vs. 143± 2.7 mmHg, P < 0.05, n= 5) in intact male mice. 2-ME did not alter water consumption and urine osmolality, but reduced urine output and sodium excretion, and proteinuria (14.4±2.0 vs. 6.0±0.5 mg/24 hrs) in intact Cyp1b1 +/+ male mice. Treatment with 2-ME attenuated Ang II-induced end-organ damage (actin and collagen accumulation) in OVX Cyp1b1 +/+ and Cyp1b1 -/- female and Cyp1b1 +/+ male mice. 2-ME mitigated urinary excretion of angiotensinogen in OVX Cyp1b1 +/+ and Cyp1b1 -/- female mice infused with Ang II. These data suggest that 2-ME reduces Ang II- induced hypertension and associated renal dysfunction and end-organ damage in OVX Cyp1b1 +/+ and Cyp1b1 -/- female, and intact male mice. Therefore, 2-ME could serve as a therapeutic agent for treatment of hypertension and associated pathogenesis in post-menopausal females, and intact males.

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Abstract 250: 6β-hydroxytestosterone, A Cytochrome P450 1b1-derived Metabolite Of Testosterone, Mediates Increase In Thirst, Renal Dysfunction, And End Organ Damage Associated With Angiotensin II-induced Hypertension In Male Mice

Hypertension ◽

10.1161/hyp.64.suppl_1.250 ◽

2014 ◽

Vol 64 (suppl_1) ◽

Author(s):

Ajeeth K Pingili ◽

Mehmet Kara ◽

Brett L Jennings ◽

Anne M Estes ◽

Kafait U Malik

Keyword(s):

Oxidative Stress ◽

Renal Function ◽

Cytochrome P450 ◽

Renal Fibrosis ◽

Organ Damage ◽

Ang Ii ◽

Male Mice ◽

End Organ Damage ◽

Cytochrome P450 1B1 ◽

Induced Hypertension

Recently, we showed that 6β-hydroxytestosterone (6β-OHT), a cytochrome P450 1B1 (CYP1B1)-derived metabolite of testosterone, contributes to the development of angiotensin II (Ang II)-induced hypertension and associated cardiovascular pathophysiology. In view of the critical role of Ang II in renal homeostasis and end organ damage, we determined the contribution of 6β-OHT to Ang II actions on water consumption and renal function in male Cyp1b1 +/+ and Cyp1b1 -/- mice. Eight weeks old male Cyp1b1 +/+ and Cyp1b1 -/- intact or castrated mice were injected with 6β-OHT (15 μg/g, i.p. every 3 rd day) or vehicle (DMSO, 50 μl), and infused with Ang II (700 ng/kg/min) or vehicle for 2 weeks. Urine was collected for 24 hours on the final day of experiment. Castration attenuated Ang II-induced increase in water consumption and urine output, proteinuria and decrease in osmolality in both Cyp1b1 +/+ , and Cyp1b1 -/- mice (Table 1). 6β-OHT did not alter Ang II-induced increase in water intake, urine output, proteinuria and decrease in osmolality in Cyp1b1 +/+ mice, but restored these effects of Ang II in Cyp1b1 -/- or castrated mice (Table 1). Cyp1b1 gene disruption or castration prevented Ang II-induced renal fibrosis, inflammation, and oxidative stress. 6β-OHT did not alter Ang II-induced renal fibrosis, inflammation or oxidative stress in Cyp1b1 +/+ mice, however in Cyp1b1 -/- or castrated mice it restored these effects of Ang II. These data suggest that 6β-OHT, contributes to increased thirst, impairment of renal function and end organ damage associated with Ang II-induced hypertension in male mice, and that CYP1B1 could serve as a novel target for the treatment of renal disease and hypertension.

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Abstract P155: B Cells Are Not Necessary for the Developmentof Ang II-induced Hypertension and End-Organ Damage

Hypertension ◽

10.1161/hyp.72.suppl_1.p155 ◽

2018 ◽

Vol 72 (Suppl_1) ◽

Author(s):

Yuhan Chen ◽

Bethany L Dale ◽

Arvind K Pandey ◽

Matthew R Alexander ◽

Fanny Laroumanie ◽

...

Keyword(s):

B Cells ◽

Organ Damage ◽

Ang Ii ◽

End Organ Damage ◽

Induced Hypertension

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The complement receptor C5aR1 contributes to renal damage but protects the heart in angiotensin II-induced hypertension

AJP Renal Physiology ◽

10.1152/ajprenal.00040.2016 ◽

2016 ◽

Vol 310 (11) ◽

pp. F1356-F1365 ◽

Cited By ~ 20

Author(s):

Sebastian Weiss ◽

Alva Rosendahl ◽

Daniel Czesla ◽

Catherine Meyer-Schwesinger ◽

Rolf A. K. Stahl ◽

...

Keyword(s):

Cardiac Fibrosis ◽

Cardiac Injury ◽

Organ Damage ◽

Innate Immune ◽

Ang Ii ◽

End Organ Damage ◽

Induced Hypertension ◽

Infiltrating Cells ◽

Deficient Mice

Adaptive and innate immune responses contribute to hypertension and hypertensive end-organ damage. Here, we determined the role of anaphylatoxin C5a, a major inflammatory effector of the innate immune system that is generated in response to complement activation, in hypertensive end-organ damage. For this purpose, we assessed the phenotype of C5a receptor 1 (C5aR1)-deficient mice in ANG II-induced renal and cardiac injury. Expression of C5aR1 on infiltrating and resident renal as well as cardiac cells was determined using a green fluorescent protein (GFP)-C5aR1 reporter knockin mouse. Flow cytometric analysis of leukocytes isolated from the kidney of GFP-C5aR1 reporter mice showed that 28% of CD45-positive cells expressed C5aR1. Dendritic cells were identified as the major C5aR1-expressing population (88.5%) followed by macrophages and neutrophils. Using confocal microscopy, we detected C5aR1 in the kidney mainly on infiltrating cells. In the heart, only infiltrating cells stained C5aR1 positive. To evaluate the role of C5aR1 deficiency in hypertensive injury, an aggravated model of hypertension was used. Unilateral nephrectomy was performed followed by infusion of ANG II (1.5 ng·g−1·min−1) and salt in wild-type ( n = 34) and C5aR1-deficient mice ( n = 32). C5aR1-deficient mice exhibited less renal injury, as evidenced by significantly reduced albuminuria. In contrast, cardiac injury was accelerated with significantly increased cardiac fibrosis and heart weight in C5aR1-deficient mice after ANG II infusion. No effect was found on blood pressure. In summary, the C5a:C5aR1 axis drives end-organ damage in the kidney but protects from the development of cardiac fibrosis and hypertrophy in experimental ANG II-induced hypertension.

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Abstract 070: AntagomiR-762 Prevents Angiotensin II Induced Aortic Fibrosis and Stiffening

Hypertension ◽

10.1161/hyp.66.suppl_1.070 ◽

2015 ◽

Vol 66 (suppl_1) ◽

Author(s):

Kim Ramil C Montaniel ◽

Jing Wu ◽

Matthew R Bersi ◽

Liang Xiao ◽

Hana A Itani ◽

...

Keyword(s):

Angiotensin Ii ◽

Organ Damage ◽

Matrix Proteins ◽

Locked Nucleic Acid ◽

Ang Ii ◽

End Organ Damage ◽

Acid Inhibitor ◽

Vascular Stiffening ◽

Aortic Stiffening

We and others have shown that hypertension (HTN) is associated with a striking deposition of collagen in the vascular adventitia. This causes vascular stiffening, which increases pulse wave velocity and contributes to end-organ damage. Through a screen of vascular microRNAs (miRNAs), we found that miR-762 is the most upregulated miRNA in mice with angiotensin II (Ang II)-induced HTN. qRT-PCR confirmed that miR-762 is upregulated 6.35±1.22 (p=0.03) fold in aortas of Ang II-infused mice compared with controls. This was a direct effect of Ang II, as miR-762 upregulation was not eliminated by lowering blood pressure with hydralazine and hydrochlorothiazide and was increased only 2-fold in DOCA salt HTN. To study the role of miR-762 in HTN, we administered a locked nucleic acid inhibitor of miR-762 (antagomiR-762). AntagomiR-762 administration did not alter the hypertensive response to Ang II, yet it normalized stress-strain relationships and aortic energy storage that occurs in systole (Table). Further studies showed that antagomiR-762 dramatically affected vascular matrix proteins, reducing mRNA for several collagens and fibronectin and dramatically upregulating collagenases MMP1a, 8 and 13 (Table). Thus, miR-762 has a major role in modulating vascular stiffening and its inhibition dramatically inhibits pathological fibrosis, enhances matrix degradation and normalizes aortic stiffness. AntagomiR-762 might represent a new approach to prevent aortic stiffening and its consequent end-organ damage.

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Abstract 252: 6ß-Hydroxytestosterone, A Cytochrome P450 1B1 Metabolite of Testosterone, Enhances Angiotensin II-Induced Pressor Effect in Male Mice

Hypertension ◽

10.1161/hyp.62.suppl_1.a252 ◽

2013 ◽

Vol 62 (suppl_1) ◽

Author(s):

Ajeeth K Pingili ◽

Brett L Jennings ◽

Nayaab S Khan ◽

Kafait U Malik

Keyword(s):

Cytochrome P450 ◽

Endothelial Dysfunction ◽

Ros Production ◽

Oxygen Species ◽

Pressor Effect ◽

Ang Ii ◽

Male Mice ◽

Cytochrome P450 1B1 ◽

Induced Hypertension ◽

Novel Target

Androgens have been implicated in the development of hypertension and castration minimizes the pressor effect of angiotensin (Ang) II. Previously we showed that Ang II-induced hypertension and associated pathophysiological changes are diminished in male cytochrome P450 (CYP) 1B1 gene disrupted mice. Since CYP1B1 metabolizes testosterone to 6β-hydroxytestosterone (6β-OHT); this study was conducted to determine its contribution in modulation of Ang II-induced hypertension. Eight weeks old male Cyp1b1+/+ and Cyp1b1-/- mice were either castrated or injected with 6β-OHT (15 μg/g, i.p. every 3rd day) or vehicle (DMSO, 50 μl), infused with Ang II (700 ng/kg/min) or vehicle for 2 weeks, and systolic blood pressure (SBP) was measured by tail cuff. Castration attenuated Ang II-induced increase in SBP in both Cyp1b1+/+ (184 ± 6 vs. 129 ± 4 mmHg, P < 0.05) and Cyp1b1-/- mice (150 ± 6 vs. 129 ± 4 mmHg, P < 0.05). In Cyp1b1+/+ mice, 6β-OHT did not alter Ang II-induced increase in SBP (184 ± 6 vs. 180 ± 8 mmHg, P < 0.05), but enhanced it in Cyp1b1-/- mice (150 ± 6 vs. 172 ± 8 mmHg, P < 0.05). Castration improved endothelial dysfunction associated with Ang II-induced hypertension in Cyp1b1+/+ mice, as demonstrated by increased relaxation of the aorta to acetylcholine. No endothelial dysfunction was observed in Cyp1b1-/- mice given Ang II with or without castration. In Cyp1b1+/+ mice, 6β-OHT did not alter Ang II-induced endothelial dysfunction, however, in Cyp1b1-/- mice infused with Ang II, 6β-OHT caused endothelial dysfunction. We have shown that Ang II-induced hypertension is associated with increased vascular production of reactive oxygen species (ROS) in Cyp1b1+/+ mice, and this increase is attenuated in Cyp1b1-/- mice, as measured by dihydroethidium fluorescence. In both Cyp1b1+/+ and Cyp1b1-/- mice given Ang II, castration abolished the increased ROS production. In Cyp1b1+/+ mice, 6β-OHT did not alter levels of ROS produced by Ang II, however, 6β-OHT further increased ROS production in Cyp1b1-/- mice given Ang II. These data suggest that 6β-OHT, a CYP1B1 metabolite of testosterone, contributes to the hypertensive effect of Ang II in male mice. Moreover, CYP1B1 could serve as a novel target for the development of agents for the treatment of androgen-mediated hypertension.

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GANGGUAN FUNGSI GINJAL PADA IBU HAMIL PREEKLAMPSIA BERAT DENGAN DISLIPIDEMIA DI RSUD KELAS B SERANG

Jurnal Kesehatan Reproduksi ◽

10.22435/kespro.v11i1.2560 ◽

2020 ◽

Vol 11 (1) ◽

pp. 69-79

Author(s):

Muttia Amalia ◽

Erna Harfiani ◽

Aulia Chairani

Keyword(s):

Logistic Regression ◽

Renal Function ◽

Endothelial Dysfunction ◽

Sampling Technique ◽

Blood Lipid ◽

Organ Damage ◽

Blood Lipid Profile ◽

Cross Sectional ◽

End Organ Damage ◽

Class B

Abstract Background: Preeclampsia is one of the leading causes of maternal-fetal morbidity and mortality in developing countries. Dyslipidemia in severely preeclamptic women will develop end-organ damage due to endothelial dysfunction. Objective: The objective of this study was to evaluate the correlation between blood lipid profile and renal function in severely preeclamptic women at RSUD Class B Serang district, January-December 2018. Method: This study was an analytical observational study with a cross-sectional design. Conducted using total sampling technique, 103 pregnant women were included from medical records. Data were analyzed using correlation tests and logistic regression. Result: Correlation analysis indicates that HDL level (<60mg/dL) and LDL level (>160 mg/dL) had a significant impact in the alteration of urea and creatinine level in severe PE. Logistic regression analysis signifies that only decreased level of HDL had a significant partial impact on increasing creatinine levels (p=0,013 OR=1,107). Conclusion: The conclusion of this study was in severe PE women there was an increased level of TG and LDL, with a decreased level of HDL. Dyslipidemia in severe PE women will lead to oxidative stress and endothelial dysfunction, which further will cause alteration in glomerulus structure and disturbance of renal function. Keywords: dyslipidemia, creatinine, severe PE, urea Abstrak Latar Belakang: Preeklampsia (PE) merupakan salah satu penyebab utama kesakitan dan kematian ibu dan bayi di negara berkembang. Dislipidemia pada ibu hamil dengan preeklampsia berat (PEB) akan menyebabkan end-organ damage akibat disfungsi endotel. Tujuan: Tujuan penelitian ini adalah untuk menilai hubungan antara profil lipid darah terhadap gangguan fungsi ginjal pada ibu hamil dengan preeklampsia berat di RSUD Kelas B Serang periode Januari – Desember 2018. Metode: Penelitian ini merupakan penelitian observasi analitik dengan pendekatan cross sectional. Menggunakan teknik total sampling, sebanyak 103 sampel diambil dari data rekam medik. Data dianalisis menggunakan uji korelasi dan regresi logistik. Hasil: Hasil korelasi menunjukkan bahwa kadar HDL yang lebih rendah (<60 mg/dL) dan kadar LDL yang lebih tinggi (>160 mg/dL) memiliki hubungan yang bermakna terhadap peningkatan kadar ureum dan kreatinin pada bumil dengan PEB. Analisis regresi logistik memperlihatkan bahwa hanya kadar HDL yang menurun memiliki hubungan parsial yang signifikan terhadap peningkatan kadar kreatinin (p=0,013 OR=1,107). Kesimpulan: Kesimpulan penelitian ini bahwa telah ditemukan peningkatan kadar trigliserida (TG) dan LDL serta penurunan kadar HDL pada bumil dengan PEB. Dislipidemia pada PEB akan menyebabkan stres oksidasi dan disfungsi endotel yang selanjutnya akan menyebabkan perubahan struktur glomerulus dan perubahan fungsi ginjal Kata kunci: dislipidemia, kreatinin, PEB, ureum

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Abstract 649: Endothelial-derived Sphingolipids Preserve Systemic Vascular Function And Blood Pressure

Hypertension ◽

10.1161/hyp.64.suppl_1.649 ◽

2014 ◽

Vol 64 (suppl_1) ◽

Author(s):

Anna Cantalupo ◽

Yi Zhang ◽

Hideru Obinata ◽

Syvain Galvain ◽

Xiang-Cheng Jiang ◽

...

Keyword(s):

Blood Pressure ◽

Cardiovascular Diseases ◽

Endothelial Dysfunction ◽

Vascular Function ◽

Molecular Mechanisms ◽

De Novo ◽

Critical Event ◽

Ang Ii ◽

Serine Palmitoyltransferase ◽

Induced Hypertension

Endothelial dysfunction is a critical event in many cardiovascular diseases including hypertension. Although lipid signaling is implicated in endothelial dysfunction and cardiovascular diseases, specific molecular mechanisms are poorly understood. Here we report a novel regulation of endothelial sphingolipid synthesis by Nogo-B, membrane protein of the endoplasmic reticulum that modulates local sphingolipid production with direct effects on vascular function and blood pressure. Nogo-B inhibits serine palmitoyltransferase, rate-limiting enzyme of the sphingolipid de novo synthesis, controlling endothelial sphingosine 1-phosphate production and its autocrine G-protein-coupled receptor-dependent signaling actions. Mice lacking Nogo-B are hypotensive (90.1±1.6 vs. 119.9±2.6 mmHg WT mice), resistant to Ang-II (500ng/Kg/min)-induced hypertension (150.4±2.5 vs. 108.4±1.5 mmHg, compared to WT mice, 24 days after AngII infusion), and preserve endothelial function and nitric oxide release. Pharmacological inhibition of serine palmitoyltransferase with myriocin in mice that lack Nogo-B reinstated endothelial dysfunction and Ang-II-induced hypertension (143.9±1.5 vs. 90.1±1.6 mmHg, myriocin vs. vehicle treated Nogo-A/B-/- mice). Our study identifies Nogo-B as a key inhibitor of local sphingolipid synthesis and indicates that autocrine sphingolipids signaling within the endothelium are critical for vascular function and blood pressure homeostasis.

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Abstract 46: FOXP3+ T Regulatory Lymphocytes Counteract Angiotensin II-Induced Vascular Injury

Hypertension ◽

10.1161/hyp.62.suppl_1.a46 ◽

2013 ◽

Vol 62 (suppl_1) ◽

Author(s):

Muhammad Oneeb Rehman Mian ◽

Tlili Barhoumi ◽

Marie Briet ◽

Adriana Cristina Ene ◽

Asia Rehman ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Endothelial Dysfunction ◽

T Lymphocytes ◽

Vascular Injury ◽

Mesenteric Arteries ◽

Ros Production ◽

Ang Ii ◽

Induced Hypertension ◽

Regulatory Lymphocytes

Introduction: T lymphocytes participate in the low-grade inflammatory response that causes vascular injury in angiotensin (Ang) II-induced hypertension. Ang II-induced hypertension and endothelial dysfunction are blunted in T and B lymphocyte-deficient ( Rag1 -/- ) mice, and restored with reconstitution of T cells. However, the role of T regulatory lymphocytes (Treg) in Ang II-induced vascular injury is unclear. We hypothesized that adoptive transfer of FOXP3-deficient (Scurfy) T lymphocytes vs. wild-type (WT) cells will exacerbate Ang II-induced vascular damage in Rag1 -/- mice. Methods: Eleven-week old male Rag1 -/- mice were injected IV with PBS/2% FBS (control), 10 7 WT or Scurfy T lymphocytes, and 2 weeks later underwent sham surgery or were infused with Ang II (490 ng/kg/min, s.c.) using mini-osmotic pumps for 14 days (n=3-8). Systolic (SBP) and diastolic (DBP) blood pressure were measured by telemetry. Vascular function and structure were assessed in second order mesenteric arteries by pressurized myography. Reactive oxygen species (ROS) production and fibronectin and collagen I and III expression were determined in aorta. Results: Ang II induced a 40 mmHg SBP rise in Rag1 -/- mice for all treatment groups, but DBP rise was ~10 mmHg greater for WT and Scurfy T cell-injected mice than for control mice ( P <0.01). Adoptive transfer of WT T cells restored Ang II induced-endothelial dysfunction in mesenteric arteries ( P <0.05), which was exaggerated in Scurfy T cell-injected mice ( P <0.01). Ang II induced a greater increase in ROS production in aortic perivascular fat of Scurfy T cell-injected mice compared to WT T cell-injected mice ( P <0.05). Ang II induced mesenteric artery stiffness ( P <0.01) and hypertrophic remodeling ( P <0.05) in control and Scurfy T cell-injected mice, but not in WT T cell-injected mice. Ang II increased fibronectin expression to a greater extent in the aorta of control and Scurfy T cell-injected mice compared to WT T cell-injected mice ( P <0.01). Collagen I and III content was greater in the aorta of control and Scurfy T cell-injected mice than in WT T cell-injected mice ( P <0.01), but expression was unaltered by Ang II treatment. Conclusion: Foxp3+ T regulatory lymphocytes have a protective role against Ang II-induced vascular remodeling.

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