End-organ Injury Research Articles

Lymphatic dysfunction in lupus contributes to cutaneous photosensitivity and lymph node B cell responses.

Patients with systemic lupus erythematosus (SLE) are photosensitive, developing skin inflammation with even ambient ultraviolet radiation (UVR), and this cutaneous photosensitivity can be associated with UVR-induced flares of systemic disease, which can involve increased autoantibodies and further end organ injury. Mechanistic insight into the link between the skin responses and autoimmunity is limited. Signals from skin are transmitted directly to the immune system via lymphatic vessels, and here we show evidence for potentiation of UVR-induced lymphatic flow dysfunction in SLE patients and murine models. Improving lymphatic flow by manual lymphatic drainage (MLD) or with a transgenic model with increased lymphatic vessels reduces both cutaneous inflammation and lymph node B and T cell responses, and long term MLD reduces splenomegaly and titers of a number of autoantibodies. Mechanistically, improved flow restrains B cell responses in part by stimulating a lymph node fibroblastic reticular cell-monocyte axis. Our results point to lymphatic modulation of lymph node stromal function as a link between photosensitive skin responses and autoimmunity and as a therapeutic target in lupus, provide insight into mechanisms by which the skin state regulates draining lymph node function, and suggest the possibility of MLD as an accessible and cost-effective adjunct to add to ongoing medical therapies for lupus and related diseases.

Acid-Sensing Ion Channel 1a Deficiency Drives Endocrine Hypertension in Male Mice.

Acid-sensing ion channel 1a (ASIC1a) is an H + -gated cation channel that responds to extracellular acidosis in both normal and pathological states, including ischemia, inflammation, and metabolic disturbances. While ASIC1a regulates vascular reactivity, its role in blood pressure regulation remains unclear, particularly concerning sex, aging, and disease. This study aims to investigate whether ASIC1a: 1) contributes to cardiovascular function in a sex-dependent manner; 2) plays a dynamic role in cardiovascular homeostasis with aging; and 3) modulates the development of angiotensin II-induced systemic hypertension. Radiotelemeters were implanted in 6- and 18-month-old male and female wild-type ( Asic1a +/+ ) and ASIC1a knockout ( Asic1a -/- ) mice to monitor mean arterial blood pressure and heart rate under baseline conditions and in response to angiotensin II. Blood gases, electrolytes, hormones, and end-organ injury were also assessed. Aged male Asic1a -/- mice develop hypertension driven by aldosterone excess and sympathetic overactivity, which is accompanied by cardiac hypertrophy, aortic fibrosis, and glomerular hypertrophy. Female Asic1a -/- mice remain unaffected. In male Asic1a -/- mice, hyperaldosteronism occurs independent of the renin-angiotensin system and mitigates angiotensin II-induced hypertension. Furthermore, 6-month-old male Asic1a -/- mice exhibit elevated corticosterone, hypokalemia, reduced urine osmolality, increased pulse pressure, and cardiomyocyte hypertrophy that precedes hypertension. These findings establish ASIC1a as a novel, sex-specific regulator of cardiovascular function, linking early corticosterone excess in male mice to hyperaldosteronism and implicating ASIC1a deficiency as a potential driver of endocrine-related hypertension.

Perioperative Normoxia versus Hyperoxia in Neonates with Cyanotic Heart Disease Undergoing Cardiac Surgery: A Randomized Controlled Trial.

Perioperative Normoxia versus Hyperoxia in Neonates with Cyanotic Heart Disease Undergoing Cardiac Surgery: A Randomized Controlled Trial.

Through the gap: a case series on managing Type B aortic dissection with multiple lumens and tears.

Aortic dissections are classified as Stanford Type A and B based on site of intimal dissection. Management of Type B dissections is guided by risk stratification. Complicated and high-risk Type B aortic dissections are managed either using endovascular or open surgical repair. Uncomplicated Type B dissections are managed medically. The role of the patency of the false lumen and the presence of reentry tears in the dissecting membrane are still contested. Here, we describe two cases of descending aortic dissections with varying anatomical features in the setting of cocaine use and uncontrolled hypertension. The first case uniquely had a triple lumen dissection with two true lumens, while the second case had two distal tears. Both patients initially had signs of reduced end organ perfusion that resolved with control of comorbid conditions. After multidisciplinary discussions, the decision was made to continue with anti-impulse treatment. Due to the radiological and biochemical absence of evidence of end organ injury even while visceral organs were supplied by the false lumen, our multidisciplinary team preferred conservative management with anti-impulse therapy. This serves as a demonstration of individualized management of Type B aortic dissection in patients with multiple comorbidities using carefully analyzed radiographic and biochemical evidence.

Metabolic and Proteomic Divergence is Present in Spleens and Livers from Berkeley Sickle Cell Anemia and β-Thalassemia Mice.

Sickle cell disease and β-Thalassemia are two of the most prevalent hemoglobinopathies worldwide. Both occur due to genetic mutations within the HBB gene and are characterized by red blood cell dysfunction, anemia, and end-organ injury. The spleen and liver are the primary organs where erythrophagocytosis, engulfing the red blood cells, occurs in these diseases. Understanding metabolism and protein composition within these tissues can therefore inform the extent of hemolysis and disease progression. We utilized a multiomics approach to highlight metabolomic and proteomic differences in the spleen and liver. The Berkley sickle cell disease (Berk-SS), heterozygous B1/B2 globin gene deletion (HbbTh3/+) a known β-Thalassemia model, and wildtype (WT, C57/Bl6) murine models were evaluated in this report. This analysis showed Berk-SS and HbbTh3/+ shared distinct antioxidant and immunosuppressive splenic phenotypes compared to WT mice with divergence in purine metabolism, gluconeogenesis, and glycolysis. In contrast, Berk-SS mice have a distinct liver pro-inflammatory phenotype not shared by HbbTh3/+ or WT mice. Together, these data emphasize that metabolic and proteomic reprogramming of the spleen and livers in Berk-SS and HbbTh3/+mice may be relevant to the individual disease processes.

Fibrinolytic uses in the emergency department: a narrative review.

Fibrinolytic uses in the emergency department: a narrative review.

Teasing out factors differentiating pathologic from benign pneumatosis intestinalis.

Pneumatosis intestinalis (PI) is a rare radiographic finding that can range from being a benign process to needing emergency surgery. Sufficiently powered studies are lacking, and recommendations for management remain unclear. The purpose of this study was to identify key predictors of pathologic PI using physical examination, laboratory, and radiographic findings. A retrospective cohort study was conducted at two quaternary academic centers (2010-2020). A total of 334 consecutive patients 18 years or older with radiographic evidence of PI were identified. Patients were excluded if they pursued comfort care or if there was concurrent radiographic evidence of vaso-occlusive process. Pathologic PI was defined as presence of ischemic and/or perforated bowel on exploratory laparotomy or death prior to planned surgery. Of the 334 patients included in our study, 91 (27%) underwent exploratory laparotomy, of which 59 (65%) had ischemic and/or perforated bowel. These latter patients and 10 other patients who died before exploratory laparotomy defined the pathologic PI cohort. A stepwise model was created for predicting pathologic disease. Significant predictors were the presence of portal venous gas, multisegment PI, vasopressor use, peritonitis, increasing leukocyte count, and end organ injury, which were used to construct a nomogram for clinical use. A nomogram score based on presence of portal venous gas, multisegment PI, vasopressor use, peritonitis, leukocytosis, and end organ injury may help predict the probability of pathologic PI and therefore can inform surgical decision making. Epidemiologic Study; Level III.

Association of Erythrocyte Hemolysis Products and Kidney Injury During Neonatal Cardiac Surgery

Background/Objectives: Hemolysis has been associated with acute kidney injury (AKI) in infants and neonates after surgery involving cardiopulmonary bypass (CPB). Erythrocyte hemolysis and subsequent end-organ injury have been shown to be a complex process involving the liberation of multiple molecules that mediate the loss of nitric oxide and oxidative damage. This study assesses the association of multiple products of erythrocyte hemolysis with the evolution of AKI in neonates and infants undergoing CPB surgery. Methods: Blood and urine samples were collected at multiple time points before and after CPB and stored within an institutional biorepository. Twenty-one patients with AKI were matched with twenty-one non-Aki patients based on demographic and case complexity data. Results: Samples were analyzed for cell-free hemoglobin, heme, non-transferrin-bound iron, haptoglobin, hemopexin, and nitrite/nitrate. NGAL and KIM-1 were measured to index AKI. Cell-free hemoglobin was higher, haptoglobin was lower, and haptoglobin:hemoglobin ratio was lower in AKI compared to non-AKI patients. Conclusions: AKI in neonates and infants after CPB is associated with a pre and postoperative decrease in serum haptoglobin. These results confirm the need for future studies to prevent injury from hemolysis during CPB and potentially identify at-risk patients with decreased haptoglobin levels before surgery if delay is an option.

Invasive Arterial BP Measurements in the Emergency Department-When, if Ever, is it Indicated?

Extremes of blood pressure (BP) are common among patients that visit emergency departments. In this review article, we discuss the specific indications for invasive blood pressure monitoring in the ED, particularly in the context of undifferentiated shock and hypertensive emergencies. In most cases, non-invasive techniques suffice for blood pressure monitoring, however, in certain patient presentations intermittent automated oscillometry bears significant drawbacks. The most evident drawback is the extended intervals between measurements. Invasive BP (IBP) monitoring offers a pivotal tool for patients with critical illness who require accurate, timely, blood pressure monitoring and indirectly monitors for complications involving vital organ systems. In the management of patients with critical illness or at risk for end organ injury, invasive methods that directly measure BP via arterial cannulation continues to be an established standard. Overall, evaluating patients on an individual basis, with the understanding that patients who present with extreme blood pressure values need closer monitoring, should prompt consideration of invasive methods of blood pressure monitoring.

Atypical hemolytic uremic syndrome: diagnosis, management, and discontinuation of therapy.

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy typically characterized by anemia, thrombocytopenia, and end-organ injury. aHUS occurs due to endothelial injury resulting from overactivation of the alternative pathway of the complement system. The etiology of the dysregulated complement system is either a genetic mutation in 1 or more complement proteins or an acquired deficiency due to autoantibodies. Over the past decade, advancements in our understanding of the role of complement in the pathophysiology of aHUS as well as the availability of anticomplement drugs has been a game-changer for our patients. These drugs have revolutionized the clinical course, outcome, and prognosis of this disease. Therefore, all patients in whom aHUS is suspected should undergo testing for complement genetic variants and autoantibodies. In approximately 30% to 40% of patients, a genetic variant of uncertain significance (VUS) may be identified. Such patients should undergo further testing to define the significance of the VUS. A combination of antigenic, functional, and biomarker analyses can assist in establishing the significance of the variants and thereby define the etiology in most patients. These analyses will also help to determine the duration of treatment based on the individual's genetic alteration. This review aims to shed light on the diagnosis and management of aHUS and discusses how to stratify patients to determine who can safely discontinue anticomplement therapy.

Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial

Patients with obesity-related heart failure with preserved ejection fraction (HFpEF) display circulatory volume expansion and pressure overload contributing to cardiovascular–kidney end-organ damage. In the SUMMIT trial, patients with HFpEF and obesity were randomized to the long-acting glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonist tirzepatide (n = 364, 200 women) or placebo (n = 367, 193 women). As reported separately, tirzepatide decreased cardiovascular death or worsening heart failure. Here, in this mechanistic secondary analysis of the SUMMIT trial, tirzepatide treatment at 52 weeks, as compared with placebo, reduced systolic blood pressure (estimated treatment difference (ETD) −5 mmHg, 95% confidence interval (CI) −7 to −3; P < 0.001), decreased estimated blood volume (ETD −0.58 l, 95% CI −0.63 to −0.52; P < 0.001) and reduced C-reactive protein levels (ETD −37.2%, 95% CI −45.7 to −27.3; P < 0.001). These changes were coupled with an increase in estimated glomerular filtration rate (ETD 2.90 ml min−1 1.73 m−2 yr−1, 95% CI 0.94 to 4.86; P = 0.004), a decrease in urine albumin–creatinine ratio (ETD 24 weeks, −25.0%, 95% CI −36 to −13%; P < 0.001; 52 weeks, −15%, 95% CI −28 to 0.1; P = 0.051), a reduction in N-terminal prohormone B-type natriuretic peptide levels (ETD 52 weeks −10.5%, 95% CI −20.7 to 1.0%; P = 0.07) and a reduction in troponin T levels (ETD 52 weeks −10.4%, 95% CI −16.7 to −3.6; P = 0.003). In post hoc exploratory analyses, decreased estimated blood volume with tirzepatide treatment was significantly correlated with decreased blood pressure, reduced microalbuminuria, improved Kansas City Cardiomyopathy Questionnaire Clinical Summary Score and increased 6-min walk distance. Moreover, decreased C-reactive protein levels were correlated with reduced troponin T levels and improved 6-min walk distance. In conclusion, tirzepatide reduced circulatory volume–pressure overload and systemic inflammation and mitigated cardiovascular–kidney end-organ injury in patients with HFpEF and obesity, providing new insights into the mechanisms of benefit from tirzepatide. ClinicalTrials.gov registration: NCT04847557.

Skinny fat model of metabolic syndrome induced by a high-salt/sucrose diet in young male rats.

Childhood and puberty can affect metabolism, leading to tissue injury and malfunction later in life. The consumption of high-processed foods rich in salt and sugar is increasing in middle- and high-income countries, especially among young people. It is necessary to evaluate the effects of high salt and sugar levels in the youth on most injured organs during metabolic challenges. We aimed to investigate whether high-salt/sucrose intake affects whole-body development and leads to end-organ injury. Weaned male Wistar rats were divided into two groups: a control group fed a standard diet and tap water, and an experimental group (SS) fed a standard diet and a beverage containing 1·8 % NaCl and 20 % sucrose instead of tap water. The animals were treated for 60 d, starting after weaning at 21 d of age, after which the animals were subjected to glucose and insulin tolerance tests, urine collection and heart rate monitoring and euthanised for sample collection at 81 d of age. SS showed reduced body weight gain and increased food intake of sodium/sucrose solution. Interestingly, high-salt/sucrose intake led to increased body adiposity, liver lipid inclusion, heart rate and renal dysfunction. SS exhibits increased levels of PPAR alpha to counterbalance the hypertrophy of brown adipose tissue. Our findings reveal that the SS rat model exhibits non-obvious obesity with end-organ damage and preserved brown adipose tissue function. This model closely parallels human conditions with normal BMI but elevated visceral adiposity, providing a relevant tool for studying atypical metabolic disorders.

Abstract 4146137: Cell-free DNA Analysis Profiles End-Organ Injury and Predicts Outcomes with Left Ventricular Assist Device Implantation

Introduction: Durable left ventricular assist devices (LVADs) improve survival in heart failure but carry high risks of infection, hemocompatibility-related adverse events (HRAE), and death. Current clinical tools use subjective assessments or do not incorporate changes in end-organ injury, limiting their prognostic value with these complications. Plasma cell-free DNA (cfDNA), a potential marker for systemic and tissue-specific injury, holds promise to enhance patient risk stratification and prognosis. Hypothesis: LVAD implantation decreases systemic and end-organ injury, measured by cfDNA. Goal: We aimed to assess changes in global and organ-specific injury patterns with LVAD implantation via cfDNA, and to determine if pre-LVAD cfDNA levels predict post-LVAD complications. Methods: We prospectively recruited 40 LVAD candidates and 40 healthy controls. Pre- and post-LVAD plasma samples were analyzed for nuclear cfDNA (ncfDNA) and mitochondrial cfDNA (mtcfDNA) using digital droplet PCR. Tissue-specific cfDNA levels were measured using bisulfite sequencing and a deconvolution algorithm with a DNA methylation library. Wilcoxon sign-rank tests were used to compare cfDNA levels, and log-rank tests were used to compare outcomes. The clinical outcomes were HRAE-free survival (major bleeding, stroke, device thrombosis, death), and post-LVAD infection. Random forest machine learning analysis ranked tissue-specific cfDNA to identify the tissue patterns of those who develop HRAE and those who develop infection. Results: Prior to LVAD implantation, patients had 4-fold higher ncfDNA and 2-fold higher mtcfDNA compared to healthy controls. After LVAD placement, ncfDNA (18980 vs. 10228 copies/mL, p &lt; .001) and mtcfDNA levels (1051882 vs 579609 copies/mL, p &lt; .001) nearly halved, with significant reductions in innate immune and liver cfDNA (Figure). High pre-LVAD ncfDNA levels were associated with worse HRAE-free survival (p = .035) and infection (p &lt; .001). Tissue sources important in determining HRAEs were distinct from those related to infections. Conclusion: LVAD placement significantly improves systemic and tissue-specific injury, measured by reductions in cfDNA. While pre-LVAD cfDNA levels predict both post-LVAD HRAEs and infections, the cfDNA tissue contributions influencing these outcomes are distinct. Future studies will need to validate these findings and compare cfDNA to other predictors of poor LVAD outcomes.

Complement Activation and Its Implication in the Pathophysiology of Hemolytic Anemia and Aging in Mouse Models of Sickle Cell Disease and Beta-Thalassemia

Complement Activation and Its Implication in the Pathophysiology of Hemolytic Anemia and Aging in Mouse Models of Sickle Cell Disease and Beta-Thalassemia

Perioperative Management of Pediatric Combined Heart and Liver Transplantation: A 17 year single center experience.

An increasing number of centers are undertaking combined heart and liver transplantation in adult and pediatric patients with congenital heart disease. The primary aim of this study was to describe the perioperative management of a single center cohort, identifying challenges and potential solutions. We conducted a retrospective review of all patients undergoing combined heart and liver transplantation at Stanford Children's Hospital from 2006 to 2022. Preoperative information included cardiac diagnosis, hemodynamics, and severity of liver disease. Intraoperative data included length of surgery, cardiopulmonary bypass time, and blood products transfused. Postoperative data included blood products transfused in the intensive care unit, time to extubation, length of intensive care unit stay, survival outcomes and 30-day adverse events. Eighteen patients underwent en bloc combined heart and liver transplantation at Stanford Children's Hospital from 2006 to 2022, and the majority 15 (83%) were transplanted for failing Fontan circulation with Fontan Associated Liver Disease. Median surgical procedure time was 13.4 [11.5, 14.5] h with a cardiopulmonary bypass time of 4.3 [3.9, 5.8] h. Median total blood products transfused in the operating room post cardiopulmonary bypass was 89.4 [63.9, 127.0] mLs/kg. Nine patients (50%) had vasoplegia during cardiopulmonary bypass. Activated prothrombin complex concentrates were used post cardiopulmonary bypass in 15 (83%) patients with a 30-day thromboembolism rate of 22%. Median time to extubation was 4.0 [2.8, 6.5] days, median intensive care unit length of stay 20.0 [7.8, 48.3] days and median hospital length of stay 54.0 [30.5, 68.3] days. Incidence of renal replacement therapy was 11%; however, none required renal replacement therapy by the time of hospital discharge. Neurological events within 30 days were 17% and the 30 day and 1 year survival was 89%. Perioperative challenges include major perioperative bleeding, unstable hemodynamics, and end organ injury including acute kidney injury and neurological events. Successful outcomes for en bloc combined heart and liver transplantation are possible with careful multidisciplinary planning, communication, patient selection, and integrated peri-operative management.

Review of Interleukin-6 and Cardiopulmonary Bypass-Related End-Organ Injury Along With the Potential for Mitigation With Tocilizumab.

Cardiopulmonary bypass (CPB) is essential for the conduct of open-heart procedures. While lifesaving, CPB can be associated with significant end-organ injuries believed to result from inflammatory responses triggered by the extracorporeal surfaces encountering cellular elements in the blood stream. In this review, we discuss the role of interleukin-6 (IL-6) and the potential for Tocilizumab, an anti-IL-6 receptor antibody, in mitigating these effects. We compare the inflammatory responses in CPB and cytokine storm, a clinical condition in which Tocilizumab has been effectively implemented. Finally, we examine why corticosteroids, used to reduce the morbidity of CPB, may not effectively reduce IL-6 levels.

United States Rural Residence Is Associated With Increased Acute Maternal End-organ Injury or Mortality After Birth: A Retrospective Multistate Analysis, 2007-2018

(Int J Obstet Anesth. 2023;56:103916. doi:10.1016/j.ijoa.2023.103916) The maternal mortality rate in the USA rose from 7.2 to 23.8 deaths per 100,000 live births between 1987 and 2020. This increase, along with a 200% rise in severe maternal morbidity (SMM), may be partly due to increased comorbidity among expectant mothers. However, social determinants of health also play a role, including location, race/ethnicity, and age. Analysis of national data shows that women in highly urban or rural areas face higher risks of combined SMM and mortality compared with those in smaller cities. Anesthetic choice further influences outcomes, with neuraxial analgesia linked to lower SMM rates during vaginal births. Access to such anesthesia may vary based on social determinants like rural-urban disparities. This study aims to explore differences in maternal outcomes based on residency, anesthesia type, and mode of delivery, hypothesizing that rural residents face more significant risks and disparities in anesthesia access.

Immune Thrombotic Thrombocytopenic Purpura: Pathophysiology, Diagnosis, Therapy and Open Issues.

Immune thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia, and ischemic end-organ injury due to microvascular platelet-rich thrombi. iTTP pathophysiology is based on a severe ADAMTS13 deficiency, the specific von Willebrand factor (vWF)-cleaving protease, due to anti-ADAMTS13 autoantibodies. Early diagnosis and treatment reduce the mortality. Frontline therapy includes daily plasma exchange (PEX) with fresh frozen plasma replacement and immunosuppression with corticosteroids. Caplacizumab has recently been added to frontline therapy. Caplacizumab is a nanobody that binds to the A1 domain of vWF, blocking the interaction of ultra-large vWF multimers with the platelet and thereby preventing the formation of platelet-rich thrombi. Caplacizumab reduces mortality due to ischemic events, refractoriness, and exacerbations after PEX discontinuation. Until now, the criteria for response to treatment mainly took into account the normalization of platelet count and discontinuation of PEX; with the use of caplacizumab leading to rapid normalization of platelet count, it has been necessary to redefine the response criteria, taking into account also the underlying autoimmune disease. Monitoring of ADAMTS13 activity is important to identify cases with a low value of activity (<10IU/L), requiring the optimization of immunosuppressive therapy with the addition of Rituximab. Rituximab is effective in patients with refractory disease or relapsing disease. Currently, the use of Rituximab has expanded, both in frontline treatment and during follow-up, as a pre-emptive approach. Some patients do not achieve ADAMTS13 remission following the acute phase despite steroids and rituximab treatment, requiring an individualized immunosuppressive approach to prevent clinical relapse. In iTTP, there is an increased risk of venous thrombotic events (VTEs) as well as arterial thrombotic events, and most occur after platelet normalization. Until now, there has been no consensus on the use of pharmacological thromboprophylaxis in patients on caplacizumab because the drug is known to increase bleeding risk.

Association between hospital case volume and maternal adverse events in patients with placental abruption: An analysis using a Japanese national inpatient database.

Association between hospital case volume and maternal adverse events in patients with placental abruption: An analysis using a Japanese national inpatient database.

CCR10 Deficiency Reduces Blood Pressure Elevations, End-Organ Damage, and Cutaneous Infiltration of Regulatory T Cells in a Murine Model of Hypertension

Emerging evidence suggests a key role for inflammation and immune cell activation in the pathogenesis of hypertension and its associated end-organ damage. Regulatory T cells (Tregs) function primarily to limit inflammation and are generally considered protective in hypertension. However, Treg subsets can also have tissue-specific functions and play pathogenic roles in some inflammatory diseases through mechanisms, such as limiting angiogenesis. As such, the role of Tregs and its subsets in hypertension remain unclear. Recently, we demonstrated that CCR10+ Tregs are selectively decreased in the circulation of hypertensive patients. CCR10 is a key chemokine receptor for recruitment of immune cells to the skin. Although the skin has not been well studied in hypertension, prior reports in humans demonstrate that loss of skin microvessels (microvascular rarefaction) is a putative mechanism for blood pressure (BP) elevations in hypertension. Recent evidence also suggests that Tregs can promote apoptosis of vascular smooth muscle cells and endothelial cells (ECs). Thus, we hypothesized that CCR10+ Tregs promote hypertension through skin infiltration leading to enhanced microvascular rarefaction. Herein, we demonstrate that, compared to normotensive littermates, male mice with angiotensin II (Ang II)-induced hypertension have selectively increased abundance of CCR10+ Tregs in the skin (p=0.0004) with a corresponding decrease in the circulation (p=0.003). These mice also displayed increased cutaneous levels of the CCR10 ligand CCL27 (p=0.0007), suggesting a mechanism for increased CCR10+ Treg infiltration. To test a causal role of CCR10 in hypertension, we infused Ang II in control CCR10+/+ or CCR10-deficient (CCR10−/−) mice for 4 weeks. Our results demonstrate that CCR10−/− mice exhibit significant reductions in systolic blood pressure (p=0.004), albuminuria (p=0.01), and cardiac fibrosis (p=0.04) compared to wild type mice after Ang II infusion. In addition, CCR10−/− mice had a selective decrease in Tregs in the skin (p=0.02) without change in abundance of conventional CD4+ or CD8+ T cells after Ang II. CCR10−/− mice also exhibited greater cutaneous arteriolar density (p=0.02) after Ang II, consistent with reduced skin microvascular rarefaction. Finally, using PrediXcan, we demonstrate that higher genetically predicted levels of CCR10 are associated with increased risk of hypertension in humans. Taken together, our data suggest that CCR10 promotes Ang II-induced BP elevations and associated end-organ injury, at least in part by promoting Treg recruitment to the skin leading to microvascular rarefaction. K08HL153786, 5T32HL144446-05. 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.