Impaired tolerance to the autoantigen LL-37 in acute coronary syndrome.

Background: LL-37 is the only member of the cathelicidin family of antimicrobial peptides in humans and is an autoantigen in several autoimmune diseases and in acute coronary syndrome (ACS). In this report, we profiled the specific T cell response to the autoimmune self-antigen LL-37 and investigated the factors modulating the response in peripheral blood mononuclear cells (PBMCs) of healthy subjects and ACS patients. Methods and results: The activation induced marker (AIM) assay demonstrated differential T cell profiles characterized by the persistence of CD134 and CD137, markers that impair tolerance and promote immune effector and memory response, in ACS compared to Controls. Specifically, CD8+CD69+CD137+ T cells were significantly increased by LL-37 stimulation in ACS PBMCs. T effector cell response to LL-37 were either HLA dependent or independent as determined by blocking with monoclonal antibody to either Class-I HLA or Class-II HLA. Blocking of immune checkpoints PD-1 and CTLA-4 demonstrated the control of self-reactive T cell response to LL-37 was modulated predominantly by CTLA-4. Platelets from healthy controls down-modulated CD8+CD69+CD137+ T cell response to LL-37 in autologous PBMCs. CD8+CD69+CD137+ T cell AIM profile negatively correlated with platelet count in ACS patients. Conclusions: Our report demonstrates that the immune response to the autoantigen LL-37 in ACS patients is characterized specifically by CD8+CD69+CD137+ T cell AIM profile with persistent T cell activation and the generation of immunologic memory. The results provide potentially novel insight into mechanistic pathways of antigen-specific immune signaling in ACS.

Immunization using ApoB-100 peptide-linked nanoparticles reduces atherosclerosis.

Active immunization with the apolipoprotein B-100 (ApoB-100) peptide P210 reduces experimental atherosclerosis. To advance this immunization strategy to future clinical testing, we explored the possibility of delivering P210 as an antigen using nanoparticles, given this approach has been used clinically. We first characterized the responses of T cells to P210 using PBMCs from patients with atherosclerotic cardiovascular disease (ASCVD). We then investigated the use of P210 in self-assembling peptide amphiphile micelles (P210-PAMs) as a vaccine formulation to reduce atherosclerosis in B6.129P2-Apoetm1Unc/J (ApoE-/-) mice and P210's potential mechanisms of action. We also generated and characterized a humanized mouse model with chimeric HLA-A*02:01/Kb in ApoE-/- background to test the efficacy of P210-PAM immunization as a bridge to future clinical testing. P210 provoked T cell activation and memory response in PBMCs of patients with ASCVD. Dendritic cell uptake of P210-PAM and its costaining with MHC-I molecules supported its use as a vaccine formulation. In ApoE-/- mice, immunization with P210-PAMs dampened P210-specific CD4+ T cell proliferative response and CD8+ T cell cytolytic response, modulated macrophage phenotype, and significantly reduced aortic atherosclerosis. Potential clinical relevance of P210-PAM immunization was demonstrated by reduced atherosclerosis in the humanized ApoE-/- mouse model. Our data support experimental and translational use of P210-PAM as a potential vaccine candidate against human ASCVD.

The Role of T Cells Reactive to the Cathelicidin Antimicrobial Peptide LL-37 in Acute Coronary Syndrome and Plaque Calcification.

The human cationic anti-microbial peptide LL-37 is a T cell self-antigen in patients with psoriasis, who have increased risk of cardiovascular events. However, the role of LL-37 as a T cell self-antigen in the context of atherosclerosis remains unclear. The objective of this study was to test for the presence of T cells reactive to LL-37 in patients with acute coronary syndrome (ACS). Furthermore, the role of T cells reactive to LL-37 in atherosclerosis was assessed using apoE-/- mice immunized with the LL-37 mouse ortholog, mCRAMP. Peripheral blood mononuclear cells (PBMCs) from patients with ACS were stimulated with LL-37. PBMCs from stable coronary artery disease (CAD) patients or self-reported subjects served as controls. T cell memory responses were analyzed with flow cytometry. Stimulation of PBMCs with LL-37 reduced CD8+ effector T cell responses in controls and patients with stable CAD but not in ACS and was associated with reduced programmed cell death protein 1 (PDCD1) mRNA expression. For the mouse studies, donor apoE-/- mice were immunized with mCRAMP or adjuvant as controls, then T cells were isolated and adoptively transferred into recipient apoE-/- mice fed a Western diet. Recipient mice were euthanized after 5 weeks. Whole aortas and hearts were collected for analysis of atherosclerotic plaques. Spleens were collected for flow cytometric and mRNA expression analysis. Adoptive transfer experiments in apoE-/- mice showed a 28% reduction in aortic plaque area in mCRAMP T cell recipient mice (P < 0.05). Fifty six percent of adjuvant T cell recipient mice showed calcification in atherosclerotic plaques, compared to none in the mCRAMP T cell recipient mice (Fisher's exact test P = 0.003). Recipients of T cells from mice immunized with mCRAMP had increased IL-10 and IFN-γ expression in CD8+ T cells compared to controls. In conclusion, the persistence of CD8+ effector T cell response in PBMCs from patients with ACS stimulated with LL-37 suggests that LL-37-reactive T cells may be involved in the acute event. Furthermore, studies in apoE-/- mice suggest that T cells reactive to mCRAMP are functionally active in atherosclerosis and may be involved in modulating plaque calcification.

Sex as a Determinant of Responses to a Coronary Artery Disease Self-Antigen Identified by Immune-Peptidomics.

A significant body of work implicates the adaptive immune response in atherosclerosis, the main underlying cause of coronary artery disease (CAD), yet specific antigens involved remain to be fully identified. The pathobiology of CAD is influenced by sex with many factors that may be involved in the underlying mechanisms. Given the reported sexual dimorphic nature of immune-inflammatory responses, we investigated the influence of sex on potential CAD self-antigens from acute coronary syndrome (ACS) patients using immune-precipitation of soluble HLA Class-I/peptide complexes and mass spectrometry. Relevance of identified self-antigens to atherosclerosis, the major underlying cause of CAD, was tested in the apoE-/- atherosclerotic mouse model. Soluble HLA Class-I complexes from ACS patients and self-reported controls were immune-precipitated and subjected to elution, denaturation and size-exclusion to obtain HLA-bound peptides. Peptides were then subjected to mass spectrometry and patient-unique self-peptides were grouped as common to both female and male, or unique to either sex. Three peptides common to both female and male patients (COL6A1, CDSN, and SAA2), and 2 peptides each unique to female (COL1A1 and COL5A2) or male (SAA1 and KRT 9) patients were selected and mouse homologs of the peptides were screened for self-reactive immune responses in apoE-/- mice. The screening step revealed potential sex-influenced immune responses which was associated with differential immune profiles. Based on the frequency in patient plasma, COL6A1, COL5A2, and KRT 9 peptides were then tested in immunization studies. Neither COL5A2 nor KRT 9 peptide immunization resulted in significant effects on atherosclerosis compared to controls. On the other hand, female mice immunized with COL6A1 peptide had significantly reduced atherosclerosis whereas male mice had significantly increased atherosclerosis, associated with differential immune profiles. Our study identified potential self-antigens involved in atherosclerosis using the immune peptidome of CAD patients. Altering self-reactive immune responses to COL6A1 in apoE-/- mice resulted in differential effects on atherosclerosis burden with sex as a determinant of outcome.

Sex differences in crude mortality rates and predictive value of intensive care unit-based scores when applied to the cardiac intensive care unit.

BACKGROUND: Limited data exists regarding sex differences in outcome and predictive accuracy of intensive care unit-based scoring systems when applied to cardiac intensive care unit patients. METHODS: We reviewed medical records of patients admitted to cardiac intensive care unit from 1 January 2011-31 December 2016. Sex differences in mortality rates and the performance of intensive care unit-based scoring systems in predicting in-hospital mortality were analyzed. Calibration was assessed by the Hosmer-Lemeshow test and locally weighted scatterplot smoothing curves. Discrimination was assessed using the c statistic and receiver-operating characteristic curve. RESULTS: Among 6963 patients, 2713 (39%) were women. Overall in-hospital and cardiac intensive care unit mortality rates were similar in women and men (9.1% vs 9.4%, p=0.67 and 5.9% vs 6%, p=0.88, respectively) and in age and major diagnosis subgroups. Of the scoring systems, Acute Physiology and Chronic Health Evaluation III and Sequential Organ Failure Assessment had poor calibration (Hosmer-Lemeshow p value <0.001), while Simplified Acute Physiology Score II performed better (Hosmer-Lemeshow p value 0.09), in both women and men. All scores had good discrimination (C statistics >0.8). In the subgroups of acute myocardial infarction and heart failure patients, all scores had good calibration (Hosmer-Lemeshow p>0.001) and discrimination (C statistic >0.8) while in diagnosis subgroups with highest mortality, the calibration varied among scores and by sex, and discrimination was poor. CONCLUSIONS: No sex differences in mortality were seen in cardiac intensive care unit patients. The mortality predictive value of intensive care unit-based scores is limited in both sexes and variable among different subgroups of diagnoses.

IL-7R blockade reduces post-myocardial infarction-induced atherosclerotic plaque inflammation in ApoE-/- mice.

Modulating inflammation by targeting IL-1ß reduces recurrent athero-thrombotic cardiovascular events without lipid lowering. This presents an opportunity to explore other pathways associated with the IL-1ß signaling cascade to modulate the inflammatory response post-myocardial infarction (MI). IL-7 is a mediator of the inflammatory pathway involved in monocyte trafficking into atherosclerotic plaques and levels of IL-7 have been shown to be elevated in patients with acute MI. Recurrent athero-thrombotic events are believed to be mediated in part by index MI-induced exacerbation of inflammation in atherosclerotic plaques. The objective of the study was to assess the feasibility of IL-7R blockade to modulate atherosclerotic plaque inflammation following acute MI in ApoE-/- mice. Mice were fed Western diet for 12 weeks and then subjected to coronary occlusion to induce an acute MI. IL-7 expression was determined using qRT-PCR and immuno-staining, and IL-7R was assessed using flow cytometry. Plaque inflammation was evaluated using immunohistochemistry. IL-7R blockade was accomplished with monoclonal antibody to IL-7R. IL-7 mRNA expression was significantly increased in the cardiac tissue of mice subjected to MI but not in controls. IL-7 staining was observed in the coronary artery. Plaque macrophage and lipid content were significantly increased after MI. IL-7R antibody treatment but not control IgG significantly reduced macrophage and lipid content in atherosclerotic plaques. The results show that IL-7R antibody treatment reduces monocyte/macrophage and lipid content in the atherosclerotic plaque following MI suggesting a potential new target to mitigate increased plaque inflammation post-MI.

Keratin 8 is a potential self-antigen in the coronary artery disease immunopeptidome: A translational approach.

BACKGROUND: Inflammation is an important risk factor in atherosclerosis, the underlying cause of coronary artery disease (CAD). Unresolved inflammation may result in maladaptive immune responses and lead to immune reactivity to self-antigens. We hypothesized that inflammation in CAD patients would manifest in immune reactivity to self-antigens detectable in soluble HLA-I/peptide complexes in the plasma. METHODS: Soluble HLA-I/peptide complexes were immuno-precipitated from plasma of male acute coronary syndrome (ACS) patients or age-matched controls and eluted peptides were subjected to mass spectrometry to generate the immunopeptidome. Self-peptides were ranked according to frequency and signal intensity, then mouse homologs of selected peptides were used to test immunologic recall in spleens of male apoE-/- mice fed either normal chow or high fat diet. The peptide detected with highest frequency in patient plasma samples and provoked T cell responses in mouse studies was selected for use as a self-antigen to stimulate CAD patient peripheral blood mononuclear cells (PBMCs). RESULTS: The immunopeptidome profile identified self-peptides unique to the CAD patients. The mouse homologs tested showed immune responses in apoE-/- mice. Keratin 8 was selected for further study in patient PBMCs which elicited T Effector cell responses in CAD patients compared to controls, associated with reduced PD-1 mRNA expression. CONCLUSION: An immunopeptidomic strategy to search for self-antigens potentially involved in CAD identified Keratin 8. Self-reactive immune response to Keratin 8 may be an important factor in the inflammatory response in CAD.

Noncardiovascular Disease and Critical Care Delivery in a Contemporary Cardiac and Medical Intensive Care Unit.

BACKGROUND: Noncardiovascular comorbidities and critical illness are increasing in cardiovascular intensive care units (CICUs). There are limited data comparing critical care delivery, resource utilization, and costs between contemporary CICUs and medical intensive care units (MICUs). METHODS: All CICU (n = 6967; 22 748 patient-days) and MICU (n = 10 892; 39 211 patient-days) admissions to Cedars-Sinai Medical Center, a tertiary care academic medical center, between January 2011 and December 2016 were reviewed. Both the CICU and MICU admitted patients for primary cardiovascular or medical conditions during the study period, but not for postoperative surgical care. RESULTS: Patients admitted to the CICU were more frequently older, male, and had more preexisting cardiac disease ( P < .0001). More than one-fifth (21.4%) of CICU patients had a noncardiovascular primary admission diagnosis, compared to 89.2% of MICU patients. Cardiovascular intensive care unit patients had lower Acute Physiology and Chronic Health Evaluation III scores (51.1 [19.9] vs 61.1 [24.9], P < .0001) and shorter median hospital length of stay ( P < .001), but not in-unit stay, as compared to MICU patients. Mechanical ventilation, vasopressors, inotropes, renal replacement therapy, and/or blood transfusion were required in 35.0% of CICU patients compared with 62.2% of MICU patients ( P < .0001). The unit mortality rate was lower for CICU than MICU patients (4.8% vs 13.0%, P < .0001), as was the hospital mortality rate (9.3% vs 21.6%, P < .0001). The standardized mortality ratio was 0.73 for the CICU and 0.86 for the MICU. There was no difference in the mean direct cost of care per patient-day between the CICU and MICU ($4011 USD [376] vs $3990 USD [214], P = .77). CONCLUSIONS: The burden of noncardiovascular diseases and the requirement for critical care therapies are high in contemporary CICU patients but remain lower compared to the MICU population. Our findings support the growing complexity of care in tertiary CICUs. Further studies are required to explore the association between critical care delivery and outcomes in this evolving population.

Cancellation of the Cardiac Catheterization Lab After Activation for ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: Prehospital ECG-based cardiac catheterization laboratory (CCL) activation for ST-segment-elevation myocardial infarction reduces door-to-balloon times, but CCL cancellations (CCLX) remain a challenging problem. We examined the reasons for CCLX, clinical characteristics, and outcomes of patients presenting as ST-segment-elevation myocardial infarction activations who receive emergent coronary angiography (EA) compared with CCLX. METHODS AND RESULTS: We reviewed all consecutive CCL activations between January 1, 2012, and December 31, 2014 (n=1332). Data were analyzed comparing 2 groups stratified as EA (n=466) versus CCLX (n=866; 65%). Reasons for CCLX included bundle branch block (21%), poor-quality prehospital ECG (18%), non-ST-segment-elevation myocardial infarction ST changes (18%), repolarization abnormality (13%), and arrhythmia (8%). A multivariate logistic regression model using age, peak troponin, and initial ECG findings had a high discriminatory value for determining EA versus CCLX (C statistic, 0.985). CCLX subjects were older and more likely to be women, have prior coronary artery bypass grafting, or a paced rhythm ( P<0.0001 for all). All-cause mortality did not differ between groups at 1 year or during the study period (mean follow-up, 2.186±1.167 years; 15.8% EA versus 16.2% CCLX; P=0.9377). Cardiac death was higher in the EA group (11.8% versus 3.0%; P<0.0001). After adjusting for clinical variables associated with survival, CCLX was associated with an increased risk for all-cause mortality during the study period (hazard ratio, 1.82; 95% CI, 1.28-2.59; P=0.0009). CONCLUSIONS: In this study, prehospital ECG without overreading or transmission lead to frequent CCLX. CCLX subjects differ with regard to age, sex, risk factors, and comorbidities. However, CCLX patients represent a high-risk population, with frequently positive cardiac enzymes and similar short- and long-term mortality compared with EA. Further studies are needed to determine how quality improvement initiatives can lower the rates of CCLX and influence clinical outcomes.

Early mobility in frail and non-frail older adults admitted to the cardiovascular intensive care unit.

PURPOSE: Little is known about the effects of early mobilization in older adults in the Cardiovascular Intensive Care Unit (CICU). MATERIALS AND METHODS: We reviewed consecutive patients ≥60 years of age admitted to the CICU at an academic tertiary care center from 2016 to 2017. The level of function (LOF) was assessed prehospital, at CICU admission, and at CICU transfer using a graded scale ranging from LOF 1 (bedbound) to 4 (walk > 50 ft). The prehospital frailty status was assessed using Rockwood's Clinical Frailty Scale. We sought to determine whether the mean change of LOF during CICU admission differed based on frailty status. RESULTS: There were 264 patients in the cohort (77.1 ±â€¯9.3 years old; 40% female; 34% frail). Frail patients were more likely to have lower prehospital, CICU admission, day of transfer LOFs (all P < 0.001). The mean LOF improvement during CICU stay was 0.5 ±â€¯0.8 and did not differ based on frailty status. Frailty was not predictive of EM responsiveness in the adjusted analysis. CONCLUSIONS: EM is feasible in older adults admitted to the CICU. Functional status improved in both frail and non-frail older adults during CICU admission. Prospective studies are needed to determine whether frail older adults may benefit from EM.

Systematic review and directors survey of quality indicators for the cardiovascular intensive care unit.

BACKGROUND: Quality indicators (QIs) are increasingly used in cardiovascular care as measures of performance but there is currently no consensus on indicators for the cardiovascular intensive care unit (CICU). METHODS: We searched Medline, CINAHL, EMBASE, and COCHRANE databases from inception until October 2016 and websites for organizations involved in quality measurement for QIs relevant to cardiovascular disease in an intensive or critical care setting. We surveyed 14 expert cardiac intensivist-administrators (7 European; 7 North American) on the importance and relevance of each indicator as a measure of CICU care quality using a scale of 1 (=lowest) to 10 (=highest). Indicators with a mean score ≥8/10 for both importance and relevance were included in the final set. RESULTS: Overall, 108 QIs (70 process, 18 structural, 18 outcome, 1 patient engagement, and 1 covering multiple domains) were identified in 30 articles representing 23 agencies, organizations, and societies. Disease-specific QIs included myocardial infarction (n = 37), heart failure (n = 31), atrial fibrillation (n = 11), and cardiac rehabilitation (n = 1); general QIs represented about one-quarter (n = 28) of all measures. Fifteen QIs were selected for the final QI set: 7 process, 2 structural, and 6 outcome measures, including 6 general and 9 disease-specific measures. Outcome measures chosen to evaluate general CICU performance included overall CICU mortality, length of stay, and readmission rate. CONCLUSIONS: Numerous QIs relevant to the CICU have been recommended by a variety of organizations. The indicators chosen by the cardiac intensivist-administrators could serve as a basis for future efforts to develop a standardized set of quality measures for the CICU.

The cathelicidin protein CRAMP is a potential atherosclerosis self-antigen in ApoE(-/-) mice.

Auto-immunity is believed to contribute to inflammation in atherosclerosis. The antimicrobial peptide LL-37, a fragment of the cathelicidin protein precursor hCAP18, was previously identified as an autoantigen in psoriasis. Given the reported link between psoriasis and coronary artery disease, the biological relevance of the autoantigen to atherosclerosis was tested in vitro using a truncated (t) form of the mouse homolog of hCAP18, CRAMP, on splenocytes from athero-prone ApoE(-/-) mice. Stimulation with tCRAMP resulted in increased CD8+ T cells with Central Memory and Effector Memory phenotypes in ApoE(-/-) mice, differentially activated by feeding with normal chow or high fat diet. Immunization of ApoE(-/-) with different doses of the shortened peptide (Cramp) resulted in differential outcomes with a lower dose reducing atherosclerosis whereas a higher dose exacerbating the disease with increased neutrophil infiltration of the atherosclerotic plaques. Low dose Cramp immunization also resulted in increased splenic CD8+ T cell degranulation and reduced CD11b+CD11c+ conventional dendritic cells (cDCs), whereas high dose increased CD11b+CD11c+ cDCs. Our results identified CRAMP, the mouse homolog of hCAP-18, as a potential self-antigen involved in the immune response to atherosclerosis in the ApoE(-/-) mouse model.

Early Coronary Angiography for Survivors of Out-of-Hospital Cardiac Arrests Without ST Elevation.

There are over 300,000 out-of-hospital cardiac arrests (OOHCA) in the United States each year, and the long-term survival rate is less than 10%. Despite improvements in postarrest management, the greatest drop-off in survival occurs during hospitalization, mostly due to myocardial dysfunction and neurological injury. Coronary artery disease is common in postcardiac arrest patients, with an incidence of approximately 60-80%. In patients with a chest pain syndrome and an ST-segment-elevation myocardial infarction pattern evident on the presenting electrocardiogram, immediate revascularization is recommended by cardiovascular societies due to established mortality benefits. However, it is less clear whether immediate or urgent coronary angiography for OOHCA survivors without ST elevation on the presenting electrocardiogram is beneficial. The current evidence base suggests that many OOHCA survivors, particularly when an acute coronary event is suspected, stand to benefit from early coronary angiography, although prospective trial data are lacking. Further studies are needed to identify whether all or even a subset of OOHCA survivors without ST elevation should undergo routine early coronary angiography.

Identification of apoB-100 Peptide-Specific CD8+ T Cells in Atherosclerosis.

BACKGROUND: T cells are found in atherosclerotic plaques, with evidence supporting a potential role for CD8+ T cells in atherogenesis. Prior studies provide evidence of low-density lipoprotein and apoB-100 reactive T cells, yet specific epitopes relevant to the disease remain to be defined. The current study was undertaken to identify and characterize endogenous, antigen-specific CD8+ T cells in atherosclerosis. METHODS AND RESULTS: A peptide fragment of apoB-100 that tested positive for binding to the mouse MHC-I allele H2Kb was used to generate a fluorescent-labeled H2Kb pentamer and tested in apoE-/- mice. H2Kb pentamer(+)CD8+ T cells were higher in apoE-/- mice fed an atherogenic diet compared with those fed a normal chow. H2Kb pentamer (+)CD8+ T cells in atherogenic diet-fed mice had significantly increased effector memory phenotype with a shift in Vß profile. H2Kb pentamer blocked lytic activity of CD8+ T cells from atherogenic diet-fed mice. Immunization of age-matched apoE-/- mice with the apoB-100 peptide altered the immune-dominant epitope of CD8+ T cells and reduced atherosclerosis. CONCLUSIONS: Our study provides evidence of a self-reactive, antigen-specific CD8+ T-cell population in apoE-/- mice. Immune modulation using the peptide antigen reduced atherosclerosis in apoE-/- mice.

Echo-Doppler determinants of outcomes in patients with unoperated significant mitral regurgitation in current era.

OBJECTIVE: One-half of patients with severe symptomatic mitral regurgitation (MR) do not undergo surgery due to comorbidities. We evaluated prognosticators of outcomes in patients with unoperated significant MR. METHODS: In this observational study, we retrospectively evaluated medical records of 75 consecutive patients with unoperated significant MR. RESULTS: All-cause mortality was 39% at 5 years. Non-survivors (n=29) versus survivors (n=46) were: older (77±9.8 vs 68±14, p=0.006), had higher New York Heart Association (NYHA) class (2.7±0.8 vs 2.3±0.8, p=0.037), higher brain natriuretic peptide (1157±717 vs 427±502 pg/mL, p=0.024, n=18), more coronary artery disease (61% vs 35%, p=0.031), more frequent left ventricular ejection fraction <50% (20.7% vs 4.3%, p=0.026), more functional MR (41% vs 22%, p=0.069), higher mitral E/E(') (12.7±4.6 vs 9.8±4, p=0.008), higher pulmonary artery systolic pressure (PASP; 52.6±18.7 vs 36.7±14, p <0.001), more ≥3+ tricuspid regurgitation (28% vs 4%, p=0.005) and more right ventricular dysfunction (26% vs 6%, p=0.035). Significant predictors of 5-year mortality were PASP (p=0.001) and E/E(') (p=0.011) using multivariate regression analysis. CONCLUSIONS: Patients with unoperated significant MR have high mortality. Elevated PASP and mitral E/E(') were the most significant predictors of 5-year survival in patients with unoperated significant MR. Current American College of Cardiology (ACC)/American Heart Association (AHA) guidelines provide a limited incorporation of echo-Doppler parameters in the preoperative risk stratification of patients with severe MR.

Immunization with an ApoB-100 Related Peptide Vaccine Attenuates Angiotensin-II Induced Hypertension and Renal Fibrosis in Mice.

Recent studies suggest the potential involvement of CD8+ T cells in the pathogenesis of murine hypertension. We recently reported that immunization with apoB-100 related peptide, p210, modified CD8+ T cell function in angiotensin II (AngII)-infused apoE (-/-) mice. In this study, we hypothesized that p210 vaccine modulates blood pressure in AngII-infused apoE (-/-) mice. Male apoE (-/-) mice were immunized with p210 vaccine and compared to unimmunized controls. At 10 weeks of age, mice were subcutaneously implanted with an osmotic pump which released AngII for 4 weeks. At 13 weeks of age, p210 immunized mice showed significantly lower blood pressure response to AngII compared to controls. CD8+ T cells from p210 immunized mice displayed a different phenotype compared to CD8+ T cells from unimmunized controls. Serum creatinine and urine albumin to creatinine ratio were significantly decreased in p210 immunized mice suggesting that p210 vaccine had renal protective effect. At euthanasia, inflammatory genes IL-6, TNF-α, and MCP-1 in renal tissue were down-regulated by p210 vaccine. Renal fibrosis and pro-fibrotic gene expression were also significantly reduced in p210 immunized mice. To assess the role of CD8+ T cells in these beneficial effects of p210 vaccine, CD8+ T cells were depleted by CD8 depleting antibody in p210 immunized mice. p210 immunized mice with CD8+ T cell depletion developed higher blood pressure compared to mice receiving isotype control. Depletion of CD8+ T cells also increased renal fibrotic gene expression compared to controls. We conclude that immunization with p210 vaccine attenuated AngII-induced hypertension and renal fibrosis. CD8+ T cells modulated by p210 vaccine could play an important role in the anti-hypertensive, anti-fibrotic and renal-protective effect of p210 vaccine.