Search Results (92)

Background/Objective: Sepsis remains a major cause of morbidity and mortality worldwide, making early risk stratification and prognosis critical. Vascular endothelial dysfunction is a hallmark of sepsis pathogenesis, with evidence suggesting that endothelial injury may occur early, preceding organ failure. Brachial flow-mediated dilation (FMD), a validated noninvasive ultrasound technique measuring endothelium-dependent vasodilation, serves as a surrogate marker of endothelial function, where lower FMD values reflect impaired function. This systematic review and meta-analysis aimed to evaluate the validity and quality of evidence on using FMD to measure vascular endothelial dysfunction in septic patients by comparing FMD (i) between septic patients and non-septic controls and (ii) between sepsis non-survivors and survivors. Methods: PubMed, Embase, Scopus, and Web of Science were searched until November 2024 for clinical studies assessing FMD in septic patients. A random-effects model was used for the meta-analysis, and quality of studies was assessed using the Newcastle–Ottawa Scale. Results: Eight studies were included, and seven underwent quantitative synthesis (385 septic patients, 106 non-survivors and 217 survivors). Compared with non-septic controls, septic patients demonstrated significantly lower FMD (pooled standardized mean difference (SMD) = −2.1617; 95% CI −3.8349 to −0.4885; p = 0.0113; I² = 98.2939%). Within the sepsis cohort, non-survivors showed significantly attenuated FMD compared to survivors (pooled SMD = −0.7003; 95% CI −1.1133 to −0.2873; p = 0.001; I² = 60.5593%). Conclusions: FMD shows potential as a surrogate marker of endothelial dysfunction for sepsis risk assessment, as evident by lower FMD in septic patients, particularly non-survivors. Full article

The vein of Galen malformations (VoGMs) is mainly correlated with the retention of an embryonic pattern of vascularity, inducer of vein of Galen dilation, and formation of arteriovenous communications that give rise to the risk of systemic shunting, causing cardiac dysfunction, vascular steal, and venous hypertension. This is a rare cerebral vascular malformation in the newborn, accounting for 1% of all cerebral arteriovenous malformations and occurring in approximately 1 in 25,000–50,000 live births. We review nine cases of newborns diagnosed with vein of Galen malformations (VoGMs) to assess whether this pathology demonstrates a marked improvement over the past 13 years in diagnostic accuracy, treatment approaches, and patient survival rates within our clinic. Medical treatment was focused on providing inotropic support and tightly controlled peripheral and pulmonary vasodilation with the aim of overriding the effects of high output heart failure. Most of the patients underwent liver failure and flow-mediated pulmonary hypertension, while half of the newborns expressed anomalies of the nervous system due to impaired cerebral hemodynamics. Given the unavailability of endovascular treatment in our unit, which predisposes the newborns to a higher vital risk, we recognize the importance of delivering tailored intensive care aimed at maintaining cardiorespiratory and hemodynamic stability until a curative intervention can be performed in a specialized center. Full article

Decades ago, previous studies that used non-selective ergot derivatives suggested that blockage of the α_1A-adrenergic receptor mildly increased cognition through increased blood flow to the brain due to vasodilation and, thus, could be used as a treatment for dementia. However, further studies indicated that nicergoline was non-specific and hit many different targets. Today, a similar scenario is developing with the use of non-selective α₁-AR antagonists of the quinazoline class, referred to as “osins”, as potential treatments for COVID-19/SARS, post-traumatic stress disorder, cancer, and neurodegenerative disorders, such as Parkinson’s, Alzheimer’s, and amyotrophic lateral sclerosis. While there is extensive evidence of neuroprotection from many clinical trials, the mechanism of action of quinazolines is often not α₁-AR-mediated but keyed to its glycolysis-enhancing effects through activation of the enzyme phosphoglycerate kinase 1 (PGK1). These studies have incorrectly labeled the α_1A-adrenergic receptor as an “old target” to treat Alzheimer’s and other neurocognitive diseases, hampering drug development. This review will summarize these and other studies to indicate that activation, not blockage, of norepinephrine’s actions, through α_1A-AR, mediates cognitive, memory, and neuroprotective functions that may reverse the progression of neurocognitive diseases. Full article

Background/Objectives: The remodeling of adipose tissue occurring in obesity is associated with dysregulated production of various adipokines with vasoactive properties. Among the local mediators physiologically involved in vascular homeostasis, the endothelin (ET-1) system is upregulated in obesity, leading to vasoconstriction and vascular damage. We hypothesized that in human obesity, a link might exist between changed circulating levels of vasoactive adipokines and ET-1-dependent vasoconstriction; Methods: We compared plasma concentrations of selected adipokines (Luminex assay) and the vasoactive response to blockade of endothelin type A receptors (ET_A) by BQ-123 (strain-gauge plethysmography) in lean and obese individuals; Results: Plasma levels of adipokines with deleterious vascular actions, such as chemerin, visfatin, adipsin, and leptin, were higher in obese than in lean subjects (all p < 0.05). In contrast, circulating adiponectin, an adipokine with vasoprotective properties, showed no difference between groups (p > 0.05). The blood flow response to BQ-123 was greater in obese subjects than in lean subjects (p < 0.001), indicating an obesity-associated enhancement in ET-1-mediated vasoconstriction. In the entire population, circulating chemerin showed a direct correlation with the vasodilator response to BQ-123 (r = 0.30; p = 0.01). In contrast, no significant correlation was observed between concentrations of other adipokines and the response to BQ-123 (all p > 0.05). Conclusions: In human obesity, a direct link exists between increased circulating chemerin and augmented ET-1-mediated vasoconstriction. This observation contributes to explaining the detrimental vascular actions of chemerin and supports the view that targeting this adipokine might help prevent obesity-related vasculopathy. Full article

The endothelial glycocalyx (GCX) plays a crucial role in vascular health and integrity and influences many biochemical activities through mechanotransduction, in which heparan sulfate (HS) plays a major role. Endothelin-1 (ET-1) is a potent vasoregulator that binds to the endothelin B receptor (ETB) on endothelial cells (ECs), stimulating vasodilation, and to the endothelin A receptor on smooth muscle cells, stimulating vasoconstriction. While the shear stress (SS) dependence of ET-1 and HS is well documented, there is limited research documenting the SS dependence of the ETB. Understanding the SS dependence of the ETB is crucial for clarifying the role of hemodynamic forces in the endothelin system. We hypothesize that GCX HS regulates the expression of the ETB on the EC surface in an SS-dependent manner. Human lung microvascular ECs were exposed to SS in a parallel-plate flow chamber for 12 h. Damage to the GCX was simulated by treatment with 15 mU/mL heparinase-III during SS exposure. Immunostaining and qPCR were used to evaluate changes in ET-1, ETB, and HS expression. Results indicate that ETB expression is SS sensitive, with at least a 1.3-fold increase in ETB protein expression and a 0.6 to 0.4-fold-change decrease in ETB mRNA expression under SS. This discrepancy suggests post-translational regulation. In some cases, enzymatic degradation of HS attenuated the SS-induced increase in ETB protein, reducing the fold-change difference to 1.1 relative to static controls. This implies that ETB expression may be partially dependent on HS-mediated mechanotransduction, though inconclusively. Furthermore, ET-1 mRNA levels were elevated two-fold under SS without a corresponding rise in ET-1 protein expression or significant impact from HS degradation, implying that post-translational regulation of ET-1 occurs independently of HS. Full article

Increases in flow elicit dilations in the basilar artery (BA) supplied by the posterior cerebral circulation (PCC), and ensuring efficient blood supply to the circle of Willis in which blood flow and pressure can distribute and equalize, and thus provide the appropriate supply for the daughter branches to reach certain brain areas. In contrast, increases in flow elicit constrictions in the middle cerebral artery (MCA), supplied by the anterior cerebral circulation (ACC) and regulating the blood pressure and flow in distal cerebral circulation. Mediators of flow-dependent responses include arachidonic acid (AA) metabolites and nitric oxide (NO). We hypothesized that mediators of flow-dependent responses are differentially expressed in cerebral arteries of the PCC (CA_PCC) and ACC (CA_ACC). The expressions of key enzymes of the AA pathway—cyclooxygenases (COX1/COX2), cytochrome P450 hydroxylases (Cyp450), thromboxane synthase (TXAS), thromboxane A2 (TP) receptor, prostacyclin synthase (PGIS), prostacyclin (IP) receptor (IP); neuronal nitric oxide synthase (nNOS), and endothelial nitric oxide synthase (eNOS)—in the BA and MCA from rats (n = 20) were determined by western blotting. Transcriptome analysis in CA_PCC and CA_ACC from rats (n = 25) was assessed by RNA sequencing. In BA compared to MCA, COX1/2 and Cyp450 protein expressions were lower, PGIS was higher, TXAS and nNOS/eNOS were similar, TP receptors were lower, and IP receptors were higher. Gene expressions of vasodilator canonical pathways were higher in CA_PCC; vasoconstriction canonical pathways were higher in CA_ACC. Mediators of flow-dependent vasomotor signaling are differentially expressed in cerebral arteries of the posterior and anterior circulation, corresponding to their vasomotor function. Full article

Background/Objectives: Remifentanil and dexmedetomidine are widely used agents for pain management during general anesthesia. Adropin acts as a regulator of endothelial function by affecting nitric oxide bioavailability and various hemodynamic factors, including blood flow, vascular dilatation, and mean arterial pressure. We aimed to evaluate the effects of remifentanil and dexmedetomidine on adropin and eNOS levels and hemodynamic parameters in patients undergoing unilateral single-level lumbar microdiscectomy under controlled hypotension. Methods: This study included 40 patients who underwent lumbar microdiscectomy and were randomly assigned to two groups: 20 patients received remifentanil, and 20 received dexmedetomidine. Hemodynamic parameters, preoperative and postoperative VAS scores, and intraoperative blood loss were recorded. Adropin and eNOS mRNA levels were measured with RT-qPCR at three time points: preoperative (T1), intraoperative (T2), and postoperative (T3). Adropin protein levels were evaluated using ELISA. Results: The remifentanil and dexmedetomidine groups had similar heart rate, arterial pressure, intraoperative blood loss, surgery time, and VAS scores. The extubation time was longer with remifentanil. Adropin mRNA level was higher in remifentanil at all time points. At T2, the eNOS mRNA level was higher in the remifentanil group. In the dexmedetomidine group, adropin mRNA levels decreased at T2 compared to T1. Adropin protein levels were higher in the remifentanil group at T2 and T3. In the dexmedetomidine group, serum adropin levels decreased at T3 compared to those at T1. Preoperative VAS scores in patients receiving both remifentanil and dexmedetomidine were higher than postoperative VAS scores. No significant correlation was observed between VAS scores and adropin levels or between intraoperative blood loss and adropin protein levels. Conclusions: Both drugs demonstrated similar effects on the hemodynamics of the patients, and adropin levels were not associated with the VAS score and intraoperative blood loss. These findings suggest that dexmedetomidine mediates vasodilation through adropin-independent mechanisms, while remifentanil may provide more favorable surgical conditions through adropin in patients undergoing unilateral single-level lumbar microdiscectomy. Full article

Endothelial cells respond to forces generated by laminar blood flow with changes in vasodilation, anticoagulant, fibrinolytic, or anti-inflammatory functions which preserve vessel patency. These responses to flow shear stress are primarily mediated by the modulation of the following transcription factors: Krüppel-like factors 2 and 4 (KLF2 and KLF4). Notably, disturbed flow patterns, which are found in vascular areas predisposed to atherosclerosis, significantly reduce the endothelial expression of KLF2 and KLF4, resulting in changes in the transcriptome that exacerbate inflammation and thrombosis. The endothelial CCM (Cerebral Cavernous Malformation) complex, comprising KRIT1 (Krev1 interaction trapped gene 1), CCM2 (Malcavernin), and CCM3 (Programmed cell death protein 10), suppresses the expression of KLF2 and KLF4. Loss of function of the CCM complex has recently been suggested to protect from coronary atherosclerosis in humans. We thus hypothesized that the silencing of KRIT1, the central scaffold of the CCM complex, can normalize the atherogenic effects of disturbed flow on the human endothelial transcriptome. Bulk RNA sequencing (RNA-seq) was conducted on human umbilical vein endothelial cells (HUVECs) after the expression of KRIT1 was silenced using specific small interfering RNA (siRNA). The endothelial cells were exposed to three different conditions for 24 h, as follows: pulsatile shear stress (laminar flow), oscillatory shear stress (disturbed flow), and static conditions (no flow). We found that silencing the KRIT1 expression in HUVECs restored the expression of the transcription factors KLF2 and KLF4 under oscillatory shear stress. This treatment resulted in a transcriptomic profile similar to that of endothelial cells under pulsatile shear stress. These findings suggest that inhibition of the CCM complex in endothelium plays a vasoprotective role by reactivating a protective gene program to help endothelial cells resist disturbed blood flow. Targeting CCM genes can activate well-known vasoprotective gene programs that enhance endothelial resilience to inflammation, hypoxia, and angiogenesis under disturbed flow conditions, providing a novel pathway for preventing atherothrombosis. Full article

Introduction: Tumour-associated antigens (TAA) have been implicated in cell adhesion and cancer metastasis formation, but also in inflammatory processes, such as rheumatoid arthritis (RA). There has been little information about the possible associations of TAAs with RA-related clinical and laboratory parameters, with impaired vascular pathophysiology in RA, as well as about the effects of antirheumatic drugs on TAA production. Therefore, we determined the effects of one-year tofacitinib treatment on TAA levels, as well as correlations of TAA levels with various RA-associated and vascular parameters. Patients and methods: Altogether, 26 RA patients received 5 mg bid or 10 mg bid tofacitinib treatment for 12 months. Ultrasound-based functional vascular assessments, such as common carotid intima-media thickness (ccIMT), brachial artery flow-mediated vasodilation (FMD) and carotid-femoral pulse-wave velocity (cfPWV), were determined at various timepoints. Serum concentrations of TAAs, including carcinoembryonic antigen (CEA), CA15-3, CA19-9, CA125, CA72-4, human epididymis protein 4 (HE4) and tissue polypeptide antigen (TPA), as well as various cytokines (TNF-α, IL-6, IL-8, VEGF) and PECAM-1 were determined by flow cytometry using a bead-based multiplex assay (LEGENDplex). Results: As previously determined and published, one-year tofacitinib treatment effectively suppressed disease activity and inflammation. Serum CA15-3 and HE4 levels significantly decreased both after 6 and 12 months compared to baseline (p < 0.05). CA19-9 levels significantly increased both after 6 and 12 months, while CEA levels transiently increased after 6 months versus baseline (p < 0.05). CA125, CA72-4 and TPA levels did not change over time. In various regression analyses, TAA levels showed variable, significant, positive associations with the 28-joint disease activity score (DAS28), CRP, ESR, RF, IL-6, TNF-α, IL-8 and PECAM-1 (p < 0.05). In addition, TAAs variably correlated with ccIMT and cfPWV (p < 0.05). Moreover, one-year changes in TAA levels variably correlated with DAS28, RF and some cytokines (p < 0.05), as well as with changes in DAS28, HAQ, CRP, ESR, IL-6, VEGF and ccIMT from baseline to 12 months (p < 0.05). Conclusions: JAK inhibition might decrease the levels of some TAAs and increase those of others. TAA levels might be associated with RA-related and vascular biomarkers. These results suggest that TAAs might play a role in inflammatory processes and vascular pathology underlying RA. Full article

Increasing long-term observations suggest that coronavirus disease 2019 (COVID-19) vasculopathy may persist even 1.5 years after the acute phase, potentially accelerating the development of atherosclerotic cardiovascular diseases. This study systematically reviewed the variability of brachial flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity (cfPWV) from the acute phase of COVID-19 through 16 months of follow-up (F/U). Databases including PubMed, Web of Science, MEDLINE, and Embase were screened for a meta-analysis without language or date restrictions (PROSPERO reference CRD42025642888, last search conducted on 1 February 2025). The quality of the included studies was assessed using the Newcastle–Ottawa Quality Scale. We considered all studies (interventional pre-post studies, prospective observational studies, prospective randomized, and non-randomized trials) that assessed FMD or cfPWV in adults (aged ≥ 18 years) with or after laboratory-confirmed COVID-19 compared with non-COVID-19 controls or that assessed changes in these parameters during the F/U. Twenty-one studies reported differences in FMD, and 18 studies examined cfPWV between COVID-19 patients and control groups during various stages: acute/subacute COVID-19 (≤30 days from disease onset), early (>30–90 days), mid-term (>90–180 days), late (>180–270 days), and very late (>270 days) post-COVID-19 recovery. Six studies assessed variability in FMD, while nine did so for cfPWV during the F/U. Data from 14 FMD studies (627 cases and 694 controls) and 15 cfPWV studies (578 cases and 703 controls) were included in our meta-analysis. FMD showed a significant decrease compared to controls during the acute/subacute phase (standardized mean difference [SMD]= −2.02, p < 0.001), with partial improvements noted from the acute/subacute phase to early recovery (SMD = 0.95, p < 0.001) and from early to mid-term recovery (SMD = 0.92, p = 0.006). Normalization compared to controls was observed in late recovery (SMD = 0.12, p = 0.69). In contrast, cfPWV values, which were higher than controls in the acute/subacute phase (SMD = 1.27, p < 0.001), remained elevated throughout the F/U, with no significant changes except for a decrease from mid-term to very late recovery (SMD= −0.39, p < 0.001). In the very late recovery, cfPWV values remained higher than those of controls (SMD = 0.45, p = 0.010). In the manuscript, we discuss how various factors, including the severity of acute COVID-19, the persistence of long-term COVID-19 syndrome, and the patient’s initial vascular age, depending on metrics age and cardiovascular risk factors, influenced the time and degree of FMD and cfPWV improvement. Full article

Metabolic stress on the heart can cause dilation of coronary arterioles for blood flow recruitment. Although potassium ions (K⁺) released from the myocardium are a major mediator for this response, the underlying signaling pathways for vasodilation are incompletely understood. Herein, the roles of smooth muscle inward-rectifier K⁺ channel subtype 2.1 (K_ir2.1) and Na⁺/K⁺-ATPase were examined. Porcine coronary arterioles were isolated, cannulated, and pressurized for vasomotor study. Vessels developed basal tone and dilated concentration-dependently to extraluminal K⁺ from 7 to 20 mM. Higher K⁺ concentrations (25–40 mM) caused graded vasoconstriction. Vasodilation to K⁺ (10 mM) was not altered by endothelial removal, and blockade of ATP-sensitive K⁺ channels, voltage-sensitive K⁺ channels, or calcium-activated K⁺ channels did not affect K⁺-induced vasodilation. However, sustained but not abrupt transient vasodilation to K⁺ was reduced by the nonspecific K_ir channel inhibitor Ba²⁺ or K_ir2.1 channel blocker chloroethylclonidine. The Na⁺/K⁺-ATPase inhibitor ouabain attenuated K⁺-elicited vasodilation, and ouabain with Ba²⁺ abolished the response. Transfection of arterioles with K_ir2.1 antisense oligonucleotides abolished sustained but not transient dilation. It is concluded that extraluminal K⁺ elevation within the physiological range induces initial transient dilation of porcine coronary arterioles by activating smooth muscle Na⁺/K⁺-ATPase and sustained dilation via smooth muscle K_ir2.1 channels. Full article

This narrative review provides an analysis of the role of nitric oxide (NO) and its precursors, particularly L-arginine, in vascular regulation and health, with an emphasis on findings from our experimental research in animal models. NO serves as a critical mediator of vascular function, contributing to vasodilation, the regulation of blood flow, and the prevention of thrombosis. As a primary precursor of NO, L-arginine is essential for maintaining endothelial integrity, modulating mitochondrial function, and reducing oxidative damage. This review synthesises the data and contextualises these findings within the physiological challenges faced by blood donors, such as repeated blood donation and associated oxidative stress. It examines the effects of L-arginine supplementation on mitochondrial respiration, lipid peroxidation, and microsomal oxidation in different conditions, including differences in age, gender, and dietary interventions. The mechanisms by which L-arginine enhances NO production, improves vascular elasticity, and alleviates endothelial dysfunction caused by reduced NO bioavailability are also investigated. By integrating experimental findings with insights from the existing literature, this review provides a perspective on the potential of L-arginine supplementation to address the specific physiological needs of blood donors. It highlights the importance of personalised nutritional approaches in enhancing donor recovery and vascular resilience. In addition, this review assesses the wider implications of L-arginine supplementation in mitigating oxidative stress and preserving vascular function. The interplay between NO bioavailability, dietary factors, and physiological adaptation in blood donors is highlighted, along with the identification of current knowledge gaps and recommendations for future research. By presenting both original experimental evidence and a critical synthesis of the literature, this article highlights the therapeutic potential of NO precursors, particularly L-arginine, in promoting vascular health in the context of blood donation. Full article

Background: People with HIV (PWH) are at increased risk of vascular dysfunction and cardiovascular disease (CVD). SARS-CoV-2 infection has been associated with acute CVD complications. The aim of the study was to as-sess macrovascular function as an early indicator of CVD risk in PWH after mild SARS-CoV-2 infection. Methods: PWH aged 20–60 years, with undetectable viral load (RNA < 20 copies/mL), on stable anti-retroviral therapy (≥6 months) and history of mild COVID-19 (≥30 days) without any CVD manifestations prior to enrollment were recruited. Participants were excluded if they had history of diabetes mellitus, end-stage renal disease, heart or respiratory disease. Participants were matched 1:1 to pre-pandemic PWH. A health survey, surrogate measures of CVD risk, and macrovascular function (brachial artery flow-mediated vasodilation and arterial stiffness assessments via applanation tonometry) were compared between group. Results: A total of 17 PWH and history of COVID-19 (PWH/COV+) were matched with 17 PWH without COVID-19 (PWH/COV−) pre-pandemic. Mean age (45.5 years), sex (76.5% male), body mass index (27.3), and duration of HIV infection (12.2 years) were not different between groups. Both groups had comparable CVD risk factors (total cholesterol, LDL, HDL, systolic and diastolic blood pressure). There were no differences in measures of flow mediated arterial dilatation or arterial stiffness after 30 days of SARS-CoV-2 infection. Conclusions: After recent SARS-CoV-2 infection, PWH did not demonstrate evidence of macrovascular dysfunction and increased CVD risk. Results suggest that CVD risk may not be increased in people with well-controlled HIV who did not manifest CVD complications SARS-CoV-2 infection. Full article

Background: There is compelling evidence of an inverse association between potassium intake and blood pressure (BP). A potential mechanism for this effect may be dietary potassium-mediated augmentation of endothelium-dependent relaxation. To date, studies have investigated potassium intake supplementation over several weeks in healthy volunteers with variable results on vascular function. There is no assessment of the acute vascular effects of potassium supplementation achieved by the ingestion of potassium-rich food in a hypertensive population. Objective: The purpose of this study was to investigate the effect of a high potassium meal on postprandial endothelial function as measured by flow-mediated dilatation (FMD). Methods: We performed an investigator-blinded randomized crossover trial in 33 treated hypertensive individuals. Participants consumed both a high (~2400 mg) and low (~543 mg) K⁺ meal, separated by a one-week washout period. The primary endpoint was endothelial function as assessed by FMD pre-meal and postprandially at 60 and 120 min. Meals were compared at each time point using the Hills–Armitage approach. Results: 33 individuals were included in the study (48% male, mean age 68). In the fasting state (Baseline), and at 60 min postprandial, radial artery FMD was not significantly different between the participants after consumption of either meal (baseline: high K⁺ 4.2 ± 2% versus Low K⁺ 2.6 ± 3%, p = 0.93; 60 min: high K⁺ 3.8 ± 4% versus Low K⁺ 4.1 ± 3%, p = 0.69). However, at 120 min, FMD tended to be higher in participants after the high K⁺ meal (5.2 ± 4.1%) than after the low K⁺ meal (3.9 ± 4.1%) (p = 0.07). There were no differences in participants’ radial artery diameter and blood flow between meals. Conclusions: This study does not support our hypothesis that a single high K⁺ meal improves vascular function in individuals with treated hypertension. This does not contradict the clinical evidence relating greater K⁺ intake with lower BP, but suggests that mechanistic investigations of increased K⁺ intake through diet alone and its impact on endothelial function as a mediator to reducing BP are complex and not simply due to single nutrient-mediated improvement in vascular function. Full article

Background: Small conductance Ca²⁺ activated K⁺ channels (K_Ca2.3) are important regulators of vascular function. They provide Ca²⁺-dependent hyperpolarization of the endothelial membrane potential, promoting agonist-induced vasodilation. Another important mechanism of influence may occur through positive feedback regulation of endothelial Ca²⁺ signals, likely via amplification of influx through membrane cation channels. K_Ca2.3 channels have recently been implicated in flow-mediated dilation of the arterial vasculature and may contribute to the crucial homeostatic role of shear stress in preventing vascular wall remodeling and progressive vascular disease (i.e., atherosclerosis). The impact of K_Ca2.3 channels on endothelial Ca²⁺ signaling under physiologically relevant shear stress conditions remains unknown. Methods: In the current study, we employ mice expressing an endothelium-specific Ca²⁺ fluorophore (cdh5-GCaMP8) to characterize the K_Ca2.3 channel influence on the dynamic Ca²⁺ signaling profile along the arterial endothelium in the presence and absence of shear-stress. Results: Our data indicate K_Ca2.3 channels have a minimal influence on basal Ca²⁺ signaling in the carotid artery endothelium in the absence of flow, but they contribute substantially to amplification of Ca²⁺ dynamics in the presence of flow and their influence can be augmented through exogenous positive modulation. Conclusions: The findings suggest a pivotal role for K_Ca2.3 channels in adjusting the profile of homeostatic dynamic Ca²⁺ signals along the arterial intima under flow. Full article