Female Systemic Lupus Erythematosus Mice Research Articles

Galantamine Reduces Blood Pressure and Renal Injury in Female Angiotensin II-induced Hypertensive Mice

Inflammation is a known culprit in the development and progression of hypertension. The autoimmune disease, systemic lupus erythematosus (SLE), is an important model of hypertension in the setting of chronic kidney inflammation. We have shown that administration of an acetylcholinesterase inhibitor, galantamine, attenuates the hypertension, kidney inflammation, and kidney injury in female SLE mice by activating the vagally-mediated cholinergic anti-inflammatory pathway. Although SLE hypertension represents a specific population of patients, we hypothesized that galantamine would have similar anti-inflammatory effects in the angiotensin II (AngII)-induced hypertensive mouse, which more commonly models essential hypertension. Female C57BL/6 mice were implanted with minipumps at 9 weeks of age for subcutaneous delivery of either AngII (1000 ng/kg/min) or saline (controls), and galantamine hydrobromide (4 mg/kg/day) or vehicle, for 21 days. At 12 weeks, carotid catheters were implanted and mean arterial pressure (MAP) was measured in conscious mice for two consecutive days. Mice were then euthanized, and kidneys collected. Markers of kidney inflammation and injury, including interleukin (IL)-6 and kidney injury molecule (KIM)-1, were measured by ELISA and normalized to total kidney protein. MAP (mmHg) was higher in AngII-treated mice compared to controls (174±4 vs. 133±3; n=4-5, p=0.0023). Galantamine lowered MAP in AngII mice (157±8; n=7, p=0.2567) without altering MAP in controls (133±4; n=5, p=0.9999). Renal IL-6 (pg/μg) was not different between AngII and control mice (0.004±0.0001 vs. 0.005±0.0006; p=0.6685). Although galantamine lowered IL-6 in both groups, it was only significant in controls (0.003±0.0002; p=0.0134) and not AngII mice (0.003±0.0003; p=0.4677). Renal cortical KIM-1 (pg/μg) trended higher in AngII mice compared to controls (2.53±0.50 vs 0.63±0.16; p=0.0741). Galantamine lowered KIM-1 in AngII mice (1.18±0.39, p=0.2064), but not controls (1.45 ± 0.59; p=0.6285). In summary, galantamine protected female mice from hypertension and renal injury in a model of AngII hypertension. This suggests that acetylcholinesterase inhibitor therapy may be effective in patients with hypertension. Studies funded by NIH R01HL153703 and K01HL139859 for KWM. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of Sigma-1 Receptor Activation on Renal Injury and Hypertension in Female Mice with Lupus

Systemic lupus erythematosus (SLE) is a female dominant autoimmune disease that presents with prominent renal injury and hypertension contributing to the morbidity and mortality. While the causality and association of the renal injury and hypertension is not completely understood, novel therapies to reduce these detrimental outcomes could be beneficial to SLE patients. The sigma-1 receptor is a cytoprotective ligand-regulated chaperone protein that acts by decreasing protein aggregation, cellular stress and cell death, thus preventing tissue injury. Activation of the sigma-1 receptor with pharmacological ligands enhances cytoprotection in autoimmune diseases like multiple sclerosis and Huntington’s disease; however, the efficacy of sigma-1 receptor agonists in SLE is not known. We hypothesize that sigma-1 receptor activation with the agonist, LS-1-127, will reduce renal injury and halt the progression of hypertension in SLE mice.Female SLE ( NZBWF1) mice and control ( NZW) mice were weighed and urine collected via metabolic cages weekly starting at 30 weeks of age. Urinary albumin was measured via dipsticks. At 33 weeks of age, SLE and control mice were treated with the sigma-1 receptor ligand (LS-1-127; 10 mg/kg IP) or equal volume of vehicle (10% DMSO; IP) three times a week for two weeks. At 35 weeks, mean arterial pressure (MAP) was measured in conscious mice using indwelling carotid catheters for two consecutive days and then mice were euthanized. Markers of renal injury, including urinary neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and creatinine were measured by ELISA.Body weight (g) was not different in SLE vs. control mice (39.2 ± 2.9 vs. 35.4 ± 0.9; p=0.44) and LS-1-127 did not alter body weight in SLE mice (39.1 ± 2.2; p=0.97) or controls (34.1 ± 0.6; p=0.84). Albuminuria was present in 44.4% (4 out of 9) of SLE/Veh mice and none of the controls. LS-1-127 did not improve albuminuria in SLE mice (50%; 3 out of 6). MAP (mmHg) was higher in SLE mice compared to control mice (146 ± 4 vs. 123 ± 3; n=9-10, p <0.0001). LS-1-127 did not significantly alter MAP in SLE mice (150± 8; n=6) or controls (124 ± 2; n=10). The NGAL-to-creatinine ratio (ng/mg) was higher in the SLE mice compared to controls (327.3±119.8 vs 63.2±4.3, n=9-12, p<0.0007). LS-1-127 treatment did not significantly alter the NGAL-to-creatinine ratio in SLE mice (484.3±209.0, n= 6) or control mice (71.7 ± 5.2, n=10). The KIM1-to-creatinine ratio (ng/mg) was not significantly different between any of the groups.In conclusion, two weeks of sigma-1 receptor activation with LS-1-127 did not significantly alter blood pressure or renal injury in female SLE mice with advanced disease. Further inquiry into the effect of LS-1-127 on the expression of various cellular stress markers in the kidney will be conducted. Also sigma-1 receptor activation at different stages of SLE disease progression warrants investigation. NIH (R01HL153703, K01HL139859) and Department of Defense (LR210096) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Renal TLR7 expression is associated with renal injury in female mouse model of systemic lupus erythematosus

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disorder associated with exaggerated immune activation, autoantibody production, and immune complex formation. SLE patients are predominantly women of reproductive age that often present with end organ damage, specifically in the kidneys, and hypertension. This detrimental sequelae is likely due to deposition of the immune complexes and the resulting inflammation, but the exact mechanisms are unknown. It is known however that immune complexes activate toll like receptors (TLRs) on immune cells and TLR7 particularly is known to promote the development and acceleration of the pathogenesis of SLE. Therefore, we hypothesized that renal TLR7 drives the renal injury and hypertension in female SLE mice.MethodsDouble‐stranded DNA (dsDNA) autoantibodies, a hallmark of SLE, and albuminuria, a marker of renal injury, were monitored at 30 and 35 weeks of age in female and male SLE (NZBWF1) and control (NZW) mice. Glomerular filtration rate (GFR) was measured by sinistrin clearance and renal TLR7 and tumor necrosis factor (TNF)‐α expression were measured via Western blot to assess renal function and renal inflammation at the end of 35 weeks. Mean arterial pressure was also measured in conscious mice at 35 weeks of age using indwelling arterial catheters.ResultsAt 30 weeks, female SLE mice had elevated plasma dsDNA autoantibodies compared to female controls (4.6e5 ± 1.3e5 vs 8.9e4 ± 3.3e4; n=3‐5; all p<0.05), male SLE mice (6.3e4 ± 2.7e4 U/mL), and male controls (4.8e4 ± 9.3e3). At 30 weeks, 32% (7 out of 22) of female SLE mice had albuminuria versus 5% (1 out of 22) of female controls, 5% (1 out of 20) of male SLE, and no male controls. At 35 weeks, 63% (10 out of 16) of female SLE mice had albuminuria versus 5% (1 out of 22) of female controls, 5% (1 out of 19) of male SLE, and no male controls. GFR was lower in female SLE mice compared to males at this same time point (865 ± 77 vs. 1066 ±60 μL/min/100 g body weight; p=0.029). Female SLE mice expressed a significantly higher renal cortical expression of TLR7 (3.9e5 ± 8.0e4 intensity units) than both female control (7.5e4 ± 2.6e3 intensity units; p < 0.001) and male SLE mice (7.0e4 ± 1.5e4 intensity units; p < 0.001). Renal cortical expression of TNF‐α, a downstream effector of TLR7, was increased in female SLE mice (1.3e6 ± 3.7e5 intensity units) when compared to both female control mice (1.2e5 ± 3.4e4 intensity units; p < 0.001) and male SLE mice (5.1e5 ± 1.6e5 intensity units; p < 0.001). Both female and male SLE mice were hypertensive at 35 weeks: blood pressure was higher in female SLE than female controls (152 ± 5 vs. 126 ± 3 mmHg; n=6‐8; p=0.003) and in male SLE compared to male controls (152 ± 4 vs. 136 ± 4 mmHg; n=6‐11; p=0.041).ConclusionThese data indicate that increased expression of renal TLR7 and TNF‐α is associated with renal injury and hypertension in female SLE mice. In addition, these data suggest a potential sex difference in the pathogenesis of SLE in males. Therapeutic strategies targeting the TLR7 molecular pathway should be further investigated in both female and male lupus nephritis.

Early Life Stress in Summer Months Accelerates the Progression of Autoimmunity in Female Lupus‐Prone Mice

Systemic lupus erythematosus (SLE) is a classic autoimmune inflammatory disorder in which a loss of tolerance causes over-activation of B and T cells that results in autoantibody production. These “self-attacking” autoantibodies [e.g., double-stranded (ds) DNA autoantibodies] are a hallmark of SLE and correlate with disease severity. Although it is thought that a mix of genetic, environmental, immunoregulatory, hormonal and/or epigenetic factors may initiate the autoimmune process, the exact cause of this aberrant immune activity is unknown. Our lab has worked with an established mouse model of SLE, the female NZBWF1 mouse, for over 10 years. Our SLE mice endure the stressful trek from Jackson Labs in Bar Harbor, ME to our campus in Fort Worth, TX early in life (<6 weeks of age), age in our animal facility, and remain untouched usually until 30-35 weeks of age when renal inflammation, renal injury and hypertension are prevalent. Historically, we have used the NZBWF1 mouse to determine mechanisms involved in hypertension induced by chronic renal inflammation. In doing so, we have observed that different cohorts of female SLE mice have different ranges of urinary albumin (measured via dipstick) and mortality by 34-35 weeks of age. We hypothesize that the difference in disease progression is dependent upon the season in which the mice were subjected to travel stress early in life. We retrospectively analyzed data from our published and unpublished studies and separated naïve female SLE mice from these studies into two groups based on their month of travel and arrival to our campus: winter (October-March; n = 51) and summer (April-September; n = 38). Plasma dsDNA autoantibodies at 34-35 weeks of age was higher in mice that traveled and arrived in Texas in summer months versus winter months (6.0e5 ± 8.6e4 vs. 4.1e5 ± 5.1e4 U/mL; p = 0.049). Urinary albumin (measured via ELISA), an index of renal injury, was higher in SLE mice that arrived in summer months versus winter months (13.5e3 ± 3.0e3 vs. 5.8e3 ± 1.5e3 ug/mL; p = 0.0137). Mean arterial pressure was not significantly different between the groups (144 ± 3 vs. 140 ± 2 mmHg; p =0.410). Our findings indicate that factors associated with long travel during the summer months (e.g., changes in temperature, humidity, and/or water intake) may accentuate the stress of travel during early life and accelerate the progression of autoimmunity in female SLE mice. Our current and future studies are critical in determining causative mechanisms involved in the development and maintenance of SLE autoimmunity. Additionally, these studies may provide insight into why SLE is predominate in certain groups that are more susceptible to early life stressors.

Abstract 075: Sex Differences in the Development of Autoimmune-Associated Hypertension

Systemic lupus erythematosus (SLE) is an autoimmune disorder with prevalent hypertension and is a novel disease model to study the link between chronic inflammation and hypertension. Because SLE is female-dominant, studies are usually conducted in female NZBWF1 mice, a well-established model of SLE. However, men are also diagnosed with SLE and the late onset and different clinical features draws interest. We hypothesize that sex differences exist in SLE and that female SLE mice have heightened disease, hypertension, and renal injury earlier than males. Female and male SLE and control ( NZW ) mice were monitored for albuminuria starting at 30 weeks of age and then at 35 weeks implanted with vascular catheters to allow measurement of blood pressure in conscious mice. At 30 weeks, female SLE mice had elevated plasma dsDNA autoantibodies, the hallmark of SLE, compared to male SLE (4.6e5 ± 1.3e5 vs. 6.3e4 ± 2.7e4 U/mL; n=3-5; all p&lt;0.05), female controls (8.9e4 ± 3.3e4), and male controls (4.8e4 ± 9.3e3). At this same time point, 32% (7 out of 22) of female SLE mice had albuminuria versus 5% (1 out of 20) of male SLE, 5% (1 out of 22) of female controls, and no male controls. Although male SLE mice did not reach similar levels of dsDNA autoantibodies as SLE females (2.0e5 ± 4.6e4 vs. 3.9e5 ± 4.3e4; n=8-13; p=0.015), by 35 weeks, the autoantibodies were increasing in SLE males (2.0e5 ± 4.6e4 vs. 6.3e4 ± 2.7e4; p=0.157) and higher than male controls (4.3e4 ± 9.3e3; p=0.046). At 35 weeks, 63% (10 out of 16) of female SLE mice had albuminuria versus 5% (1 out of 19) of male SLE, 5% (1 out of 22) of female controls, and no male controls. Importantly, both female and male SLE mice were hypertensive at 35 weeks: blood pressure was higher in female SLE than female controls (152 ± 5 vs. 126 ± 3 mmHg; n=6-8; p=0.003) and in male SLE compared to male controls (152 ± 4 vs. 136 ± 4 mmHg; n=6-11; p=0.041). These data confirm the development of hypertension and renal injury in female SLE mice and suggest that male SLE mice develop hypertension with no renal involvement. Future studies will allow us to investigate the divergent mechanisms involved in autoimmune-induced hypertension in female and male mice, which will ultimately provide clues in sex differences in hypertensive humans with underlying chronic inflammation.

Abstract P147: Changes in Renal Function Precede the Development of Hypertension in Female Mice With Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by inflammation, hypertension, renal injury, and cardiovascular disease. Kidney involvement is common to patients with SLE and renal hemodynamic dysfunction is evident in patients with active renal disease. However, little is known about early changes in renal hemodynamic function that may contribute to the pathogenesis of hypertension during SLE. We hypothesize that the loss of immunological tolerance and subsequent production of autoantibodies in SLE leads to impaired renal hemodynamic function that precedes the development hypertension. Female NZBWF1 (SLE) and female NZW (control) mice were instrumented with carotid artery and jugular vein catheters to determine MAP and glomerular filtration rate (GFR) respectively at ages 15, 20, 24, 28, 31, and 34 weeks. MAP was measured in conscious, freely-moving mice. GFR was measured by the clearance of fluorescein isothiocyanate-inulin (FITC-inulin) after achieving steady state through continuous infusion for five hours. GFR increases at 28 weeks of age followed by a significant decline by 34 weeks of age (P = 0.0127, P = 0.0001) compared to 34 and 15 weeks of age respectively, in the mice with SLE. GFR is increased in control mice by 28 weeks of age (P = 0.002) and remains unchanged at other time points. Compared with control mice, female mice with SLE have higher MAP by 34 weeks of age (P = &lt;0.0001). These data suggest that changes in renal hemodynamic function occur in female SLE mice prior to changes in MAP suggesting an important mechanistic role for autoimmunity to directly impair renal hemodynamic function and promote the development of hypertension.

DNA methylation was involved in total glucosides of paeony regulating ERα for the treatment of female systemic lupus erythematosus mice

Total glucosides of paeony (TGP) is a bioactive compound extracted from paeony roots and has been used in therapy for autoimmune diseases. However the molecular mechanism of TGP in the therapy of autoimmune diseases remains unclear. ERα has a pro-inflammatory role in SLE disease. In this study, we found that TGP treatment significantly decreased the expression of ERα by up-regulating ERα promoter methylation levels. Further investigation revealed that treatment with TGP increased the expression of DNMT in lupus mice. We also used DNA methyltransferase inhibitors to verify whether DNA methylation was involved in these process. HE staining results showed that TGP can reduce renal injury in SLE mice. Moreover, cytokines including IFN-γ, IL6 and IL12 expression and dsDNA levels in serum were inhibited by TGP treatment. These findings indicate that TGP inhibits autoimmunity in SLE mice possibly by downregulate ERα expression, which may in turn be due to its ability to regulate the methylation status of the ERα promoter.

Disruption of splenic nerve‐to‐spleen neurotransmission worsens disease outcome in a murine model of systemic lupus erythematosus

Aberrant chronic inflammation can usually be counteracted by endogenous mechanisms; however, such mechanisms may be impaired in the development of hypertension and renal injury. These anti‐inflammatory pathways involve the autonomic nervous system but it is unclear which branch is primarily responsible for quelling inflammation in chronic inflammatory conditions. The cholinergic anti‐inflammatory pathway is a compensatory mechanism thought to include a direct anatomical connection between the parasympathetic vagus and the sympathetic splenic nerve. Although this route of neurotransmission is controversial, we have evidence that stimulation of both of these nerves individually results in a decrease in the production and release of pro‐inflammatory cytokines from splenic immune cells. Our preliminary findings also indicate that chemical splenic denervation may disrupt anti‐inflammatory mechanisms, suggesting an important sympathetic component. In order to confirm this we removed the spleen from mice with systemic lupus erythematosus (SLE), a model of chronic inflammation, hypertension and renal injury, and hypothesized that splenectomy would further disrupt sympathetic neurotransmission within the cholinergic anti‐inflammatory pathway and result in worsened disease outcome. Female SLE mice were subjected to splenectomy or sham surgery (n = 10–12/group) at 31 weeks of age before being implanted with arterial catheters, blood pressure measurement and subsequently euthanization 4 weeks later. Anti‐double‐stranded autoantibodies, the hallmark of SLE, were not different amongst sham and splenectomized mice (4.8e5 ± 8.1e4 vs. 4.6e5 ± 5.4e4 activity units; p = 0.857), and neither was body weight (41.6 ± 2.0 vs. 40.1 ± 1.1 g; p = 0.497). However the incidence of albuminuria [&gt; 300 mg/dL; 42% (5 out of 12) vs. 33% (3 out of 9)] and leukocytes in the urine [50% (6 out of 12) vs. 33% (3 out of 9)] was elevated in splenectomized SLE mice compared to sham‐operated SLE mice. Although blood pressure was not different between sham‐operated and splenectomized SLE mice (131 ± 2 vs. 134 ± 7 mmHg; p = 0.815), there was an increase in mortality following splenectomy [33% (4 out of 12) vs. 10% (1 out of 10)]. In summary, although further studies are needed to confirm the effect splenectomy on inflammation in SLE mice we found that splenectomy exacerbated the progression of SLE disease. This suggests that the sympathetic component of the cholinergic anti‐inflammatory pathway may be important in combating the inflammation in SLE. Taken together, our studies on vagus nerve stimulation, splenic nerve stimulation and denervation and splenectomy in SLE mice suggest critical interactions between autonomic branches that may be impaired during chronic inflammation. Future studies may use technology like direct vagal stimulation via central injections and designer receptors exclusively activated by designer drugs (DREADDs) to further characterize the importance of these autonomic nervous system‐mediated pathways.Support or Funding InformationFunded by NIH 1K01HL139869 and the Lupus Research Alliance Novel Disease GrantThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Anti-CD3 antibody therapy attenuates the progression of hypertension in female mice with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disorder with prevalent hypertension that significantly contributes to the mortality in this patient population. Pre-clinical and clinical evidence suggests that anti-CD3 antibody therapy may attenuate the development of autoimmune diseases like SLE. However, it is unclear whether this treatment impacts the development of the prevalent hypertension associated with SLE. The present study was designed to determine whether anti-CD3 antibody treatment attenuates the progression of hypertension in female SLE mice with already established renal disease (albuminuria ≥100mg/dL). Female SLE (NZBWF1) and control (NZW) mice were administered either an antibody to CD3ε, a component of the T cell receptor complex expressed on all T cells, or IgG antibody (isotype control) for up to 4 weeks (intranasal; 25μg/week). Spleen weight was lower in SLE mice treated with anti-CD3 antibody than in IgG-treated SLE mice, suggesting that immune system hyperactivity is decreased. Circulating anti-dsDNA autoantibodies were increased in SLE mice compared to controls and were blunted in the anti-CD3-treated SLE mice. The development of hypertension was attenuated in anti-CD3 treated mice with SLE independently of changes in renal injury (assessed by urinary albumin). These data suggest anti-CD3 therapy during autoimmune disease may have added clinical benefit to attenuate cardiovascular risk factors like hypertension.

17β-Estradiol Protects Against the Progression of Hypertension During Adulthood in a Mouse Model of Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disorder with a high prevalence of hypertension and cardiovascular disease. Because SLE predominantly affects women, estrogen is commonly implicated as a contributor to SLE disease progression. Using an established mouse model of SLE (female NZBWF1), we tested whether estrogen has a causal role in the development of hypertension in adulthood. Thirty-week-old SLE and control mice (NZW/LacJ) underwent either a sham or ovariectomy (OVX) procedure. 17β-Estradiol (E2; 5 μg/mouse, twice/week, subcutaneously) was administered to a subset of OVX mice. Mean arterial pressure (in mm Hg) was increased in SLE mice (134±4 versus 119±3 in controls). Contrary to our hypothesis, OVX exacerbated the hypertension in female SLE mice (153±3; P<0.05 versus SLE sham), and repletion of E2 prevented the OVX-induced increase in blood pressure (132±2). The prevalence of albuminuria was increased in SLE mice compared with controls (37% versus 0%). OVX increased the prevalence in SLE mice (70% versus 37% in SLE shams). Repletion of E2 completely prevented albuminuria in OVX SLE mice. Renal cortical tumor necrosis factor α was increased in SLE mice compared with controls and was further increased in OVX SLE. The OVX-induced increase in renal tumor necrosis factor α expression was prevented by repletion of E2. Treatment of OVX SLE mice with the tumor necrosis factor α inhibitor, etanercept, blunted the OVX-induced increase in blood pressure (140±2) and prevalence of albuminuria (22%). These data suggest that 17β-estradiol protects against the progression of hypertension during adulthood in SLE, in part, by reducing tumor necrosis factor α.

Abstract 174: T Cells Promote the Progression of Hypertension and Renal Injury during Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disorder with prevalent hypertension and is a novel disease model to study the link between immune system activation and the development of hypertension. T cells have a central role in the pathogenesis of autoimmune disorders and were recently reported to promote angiotensin II and salt-sensitive hypertension. Despite their well known role in the pathogenesis of autoimmune disease and recent data suggesting an important role in the pathogenesis of hypertension, whether T cells mechanistically contribute to the prevalent hypertension during SLE remains unclear. In order to test this, experiments were designed to determine whether inhibition of T cell proliferation attenuates the progression of hypertension and renal injury in female SLE mice with established renal injury (albuminuria ≥ 100 mg/dL). SLE and control mice were administered either antibody to CD3, a component of the T cell receptor expressed on all T cells, or an anti-IgG isotype control for up to 4 weeks (intranasally; 25 μg/week). Splenic CD3 + CD4 + T cells were increased in SLE mice compared to controls (7.0 ± 4.2% vs. 3.1 ± 1.5% gated) and were reduced after the anti-CD3 treatment (2.4 ± 1.1% gated), likely reflecting a reduction in spleen weight. Anti-dsDNA autoantibodies characteristic to SLE were increased in vehicle-treated SLE mice compared to controls (19.8 ± 7.3 vs. 0.74 ± 0.07, n=10) and were blunted in the anti-CD3 treated SLE mice (9.7± 3.8, n=10). Blood pressure (mmHg) was increased in SLE mice compared to controls (156 ± 3 vs. 112 ± 4, p=0.001), and was lower in anti-CD3 treated SLE mice (137 ± 4; p=0.01) but not controls (117 ± 2). In anti-IgG treated SLE mice, albuminuria increased (+38.9 ± 36.8%) over the course of the study, whereas albuminuria in anti-CD3 treated SLE mice was unchanged (-2.53 ± 17.3%). Preliminary renal histology suggests that the anti-CD3 treatment attenuated the progression of glomerulosclerosis and preserved renal vascular structure (i.e., interlobular arteries, vasa recta). No renal injury was observed in the control mice. These data suggest that T cells have an important mechanistic role in the progression of autoimmune-associated hypertension, perhaps by promoting renal vascular structural changes and injury.