Hemodynamic Stimuli Research Articles

Copeptin as a diagnostic and prognostic biomarker in pediatric diseases.

Arginine vasopressin (AVP) plays a main role in maintaining the homeostasis of fluid balance and vascular tone and in regulating the endocrine stress response in response to osmotic, hemodynamic and stress stimuli. However, the difficulty in measuring AVP limits its clinical application. Copeptin, the C-terminal part of the AVP precursor, is released in an equimolar concentration mode with AVP from the pituitary but is more stable and simple to measure. Therefore, copeptin has emerged as a promising surrogate marker of AVP with excellent potential for the diagnosis, differentiation and prognosis of various diseases in recent decades. However, its application requires further validation, especially in the pediatric population. This review focuses on the clinical value of copeptin in different pediatric diseases and the prospects for its application as a potential biomarker.

A Characterization of the Cardiac Physiology and Aortic Pulse Wave Properties of Artistic Swimmers Across Competitive Levels.

The distinct physical and environmental stressors of artistic swimming (previously termed synchronized swimming) result in unique hemodynamic stimuli. Given that the hemodynamic stress associated with participation in an exercise modality drives adaptation of the heart and central vasculature, artistic swimming may produce a distinct cardiovascular phenotype. Presumably, athletes competing at the highest levels also have greater training exposure and, thus, exhibit more adaptation. The purpose of this study was to characterize cardiovascular form and function across the competitive spectrum of artistic swimmers. Cardiovascular structure and function were compared in a cross-sectional study of healthy controls, varsity, and elite artistic swimmers, using pulse wave analysis, pulse wave velocity, and echocardiographic images both at rest and during isometric handgrip exercise. Aortic stiffness was similar across all groups, as were characteristics of the decomposed aortic pressure waveform. At rest, both varsity and elite swimmers demonstrated similar systolic function compared to controls. However, peak left ventricular twist was greater in varsity and elites (controls: 8.0 ± 3.9, varsity: 12.8 ± 8.6, elites: 13.4 ± 3.9; both p < 0.02). Furthermore, elites demonstrated greater peak left ventricular radial strain (controls: 29.2 ± 9.9, varsity: 32.5 ± 10.3, elites: 53.9 ± 15.1; both p < 0.001) and longitudinal strain (controls: -16.9 ± 1.6, varsity: -16.5 ± 1.8, elites: -19.5 ± 3.2; both p < 0.04). In contrast to controls, both varsity and elite artistic swimmers demonstrated no change in peak late diastolic transmitral filling velocity (controls: Δ0.2 ± 0.04 m/s, varsity: Δ0.06 ± 0.04 m/s, elites: Δ0.05 ± 0.04 m/s) during isometric handgrip exercise (both p > 0.05), with elites demonstrating lower peak velocity than varsity swimmers, (p = 0.048) indicating preservation of diastolic function. Artistic swimmers demonstrate distinct cardiac physiology at rest and during isometric handgrip, with a greater extent of distinguishing features observed in those competing at the highest level of competition.

Impact of geometric and hemodynamic changes on a mechanobiological model of atherosclerosis

Background and Objective:In this work, the analysis of the importance of hemodynamic updates on a mechanobiological model of atheroma plaque formation is proposed. Methods:For that, we use an idealized and axisymmetric model of carotid artery. In addition, the behavior of endothelial cells depending on hemodynamical changes is analyzed too. A total of three computational simulations are carried out and their results are compared: an uncoupled model and two models that consider the opposite behavior of endothelial cells caused by hemodynamic changes. The model considers transient blood flow using the Navier–Stokes equation. Plasma flow across the endothelium is determined with Darcy’s law and the Kedem–Katchalsky equations, considering the three-pore model, which is also employed for the flow of substances across the endothelium. The behavior of the considered substances in the arterial wall is modeled with convection–diffusion–reaction equations, and the arterial wall is modeled as a hyperelastic Yeoh’s material. Results:Significant variations are noted in both the morphology and stenosis ratio of the plaques when comparing the uncoupled model to the two models incorporating updates for geometry and hemodynamic stimuli. Besides, the phenomenon of double-stenosis is naturally reproduced in the models that consider both geometric and hemodynamical changes due to plaque growth, whereas it cannot be predicted in the uncoupled model. Conclusions:The findings indicate that integrating the plaque growth model with geometric and hemodynamic settings is essential in determining the ultimate shape and dimensions of the carotid plaque.

Advances in exercise-induced vascular adaptation: mechanisms, models, and methods.

Insufficient physical activity poses a significant risk factor for cardiovascular diseases. Exercise plays a crucial role in influencing the vascular system and is essential for maintaining vascular health. Hemodynamic stimuli generated by exercise, such as shear stress and circumferential stress, directly impact vascular structure and function, resulting in adaptive changes. In clinical settings, incorporating appropriate exercise interventions has become a powerful supplementary approach for treating and rehabilitating various cardiovascular conditions. However, existing models for studying exercise-induced vascular adaptation primarily rely on in vivo animal and in vitro cellular models, each with its inherent limitations. In contrast, human research faces challenges in conducting mechanistic analyses due to ethics issues. Therefore, it is imperative to develop highly biomimetic in vitro/ex vivo vascular models that can replicate exercise stimuli in human systems. Utilizing various vascular assessment techniques is also crucial to comprehensively evaluate the effects of exercise on the vasculature and uncover the molecular mechanisms that promote vascular health. This article reviews the hemodynamic mechanisms that underlie exercise-induced vascular adaptation. It explores the advancements in current vascular models and measurement techniques, while addressing their future development and challenges. The overarching goal is to unravel the molecular mechanisms that drive the positive effects of exercise on the cardiovascular system. By providing a scientific rationale and offering novel perspectives, the aim is to contribute to the formulation of precise cardiovascular rehabilitation exercise prescriptions.

Endothelial cell dysfunction in cardiac disease: driver or consequence?

The vascular endothelium is a multifunctional cellular system which directly influences blood components and cells within the vessel wall in a given tissue. Importantly, this cellular interface undergoes critical phenotypic changes in response to various biochemical and hemodynamic stimuli, driving several developmental and pathophysiological processes. Multiple studies have indicated a central role of the endothelium in the initiation, progression, and clinical outcomes of cardiac disease. In this review we synthesize the current understanding of endothelial function and dysfunction as mediators of the cardiomyocyte phenotype in the setting of distinct cardiac pathologies; outline existing in vivo and in vitro models where key features of endothelial cell dysfunction can be recapitulated; and discuss future directions for development of endothelium-targeted therapeutics for cardiac diseases with limited existing treatment options.

Impact of daily artificial gravity on autonomic cardiovascular control following 60-day head-down tilt bed rest.

Impaired cardiovascular autonomic control following space flight or immobilization may limit the ability to cope with additional hemodynamic stimuli. Head-down tilt bedrest is an established terrestrial analog for space flight and offers the opportunity to test potential countermeasures for autonomic cardiovascular deconditioning. Previous studies revealed a possible benefit of daily artificial gravity on cardiovascular autonomic control following head-down tilt bedrest, but there is a need for efficiency in a long-term study before an artificial gravity facility would be brought to space. We hypothesized that artificial gravity through short-arm centrifugation attenuates functional adaptions of autonomic function during head-down tilt bed rest. 24 healthy persons (8 women, 33.4 ± 9.3 years, 24.3 ± 2.1 kg/m2) participated in the 60-day head-down tilt bed rest (AGBRESA) study. They were assigned to three groups, 30 min/day continuous, or 6(5 min intermittent short-arm centrifugation, or a control group. We assessed autonomic cardiovascular control in the supine position and in 5 minutes 80° head-up tilt position before and immediately after bed rest. We computed heart rate variability (HRV) in the time (rmssd) and frequency domain, blood pressure variability, and baroreflex sensitivity (BRS). RR interval corrected rmssd was reduced supine (p = 0.0358) and during HUT (p = 0.0161). Heart rate variability in the high-frequency band (hf-RRI; p = 0.0004) and BRS (p < 0.0001) decreased, whereas blood pressure variability in the low-frequency band (lf-SBP, p = 0.0008) increased following bedrest in all groups. We did not detect significant interactions between bedrest and interventions. We conclude that up to daily 30 min of artificial gravity on a short-arm centrifuge with 1Gz at the center of mass do not suffice to prevent changes in autonomic cardiovascular control following 60-day of 6° head-down tilt bed rest. Clinical Trial Registration: https://drks.de/search/en/trial/DRKS00015677, identifier, DRKS00015677.

Synchronized wearables for the detection of haemodynamic states via electrocardiography and multispectral photoplethysmography.

Cardiovascular health is typically monitored by measuring blood pressure. Here we describe a wireless on-skin system consisting of synchronized sensors for chest electrocardiography and peripheral multispectral photoplethysmography for the continuous monitoring of metrics related to vascular resistance, cardiac output and blood-pressure regulation. We used data from the sensors to train a support-vector-machine model for the classification of haemodynamic states (resulting from exposure to heat or cold, physical exercise, breath holding, performing the Valsalva manoeuvre or from vasopressor administration during post-operative hypotension) that independently affect blood pressure, cardiac output and vascular resistance. The model classified the haemodynamic states on the basis of an unseen subset of sensor data for 10 healthy individuals, 20 patients with hypertension undergoing haemodynamic stimuli and 15 patients recovering from cardiac surgery, with an average precision of 0.878 and an overall area under the receiver operating characteristic curve of 0.958. The multinodal sensor system may provide clinically actionable insights into haemodynamic states for use in the management of cardiovascular disease.

Vascular Changes in Hypertension: Is There Cell Death Involved? – A Narrative Review

"Background: Cardiovascular disease can be triggered and accelerated by hypertension and the underlying changes in the structure and function of arteries. The purpose of this review is to explore some vascular changes that occur in hypertension as a consequence of the imbalance between cell proliferation and cell death, processes that play an important role in stabilizing the thickness of the arterial wall during vascular remodeling. Methods: The authors conducted research through PubMed and Google Scholar databases using the following search formula: (hypertensive*) AND ((vascular modifications)) OR (vascular changes)) AND (cell death). Results: From 40 articles, only 17 publications were included in this study, taking into account four processes that can be preceded or followed by inflammation and depend on the interaction between local growth factors, vasoactive substances, and hemodynamic stimuli: Cell proliferation and growth; Cell migration; Cell death; Degradation or reorganization of extracellular matrix. Conclusions: To summarize, maladaptive vascular changes in hypertension can represent a major argument for prompt and maximal therapeutic intervention in patients with high cardiovascular risk. Moreover, they can represent an important step in discovering new markers of cardiovascular risk and in the development of new targeted therapies for different pathways of cellular signaling through which the reversibility of abnormal vascular changes could be obtained. "

Glomerular Hyperfiltration and Inflammation Promote Glomerular Injury in a CKD Model Induced by Reduced Kidney Mass

Renal autoregulation maintains renal blood flow and glomerular filtration rate (GFR) in a wide range of renal perfusion pressure (RPP). This mechanism is impaired in diabetes and chronic kidney disease (CKD), such that even modest increases in arterial pressure (AP) are transmitted to glomerular capillaries resulting in glomerular injury. Elevated RPP drives renal immune cell infiltration ( Hypertens. 76: 849-858, 2020). We showed that hypertensive mechanical stretch and T cell cytokine interleukin (IL)-17A synergistically promote vascular fibrosis ( Wu, Circ. Res. 114: 616-625, 2014). However, the mechanisms by which hemodynamic and inflammatory stimuli cause CKD remain poorly understood. We sought to investigate the contributions of glomerular hyperfiltration (GHF) and inflammation on glomerular damage in a mouse CKD model induced by reduced kidney mass (RKM). This model is characterized by impaired autoregulation, early onset hypertension and subsequent lymphocytic inflammation, albuminuria and glomerulosclerosis. We hypothesize that the initial rise in AP post RKM surgery promotes kidney injury through both GHF and renal inflammation. Eight-week old male 129/S6 mice were implanted with radiotelemeters. After a 10-day recovery, mice underwent sham surgery or RKM which involved uninephrectomy and partial renal artery ligation in the remaining kidney, such that the functional renal mass is reduced by ~ 2/3. AP, urine albumin, and transcutaneous GFR were measured at baseline, day (D) 3, D7, D14, D21, D28, and D56 after RKM.Immediately after RKM, GFR dropped to 30% of sham levels (Mean ± SEM in μL/min/100 g: RKM 279 ± 59 vs Sham 913 ± 61, n = 4 – 6, p &lt; 0.05, two-way ANOVA RM), consistent with the extent of renal mass ablation. The mean AP of RKM mice was identical to sham controls at baseline (115 ± 2 vs 116 ± 2 mmHg) but increased by 29 mmHg by D5 (144 ± 8 vs 112 ± 2 mmHg, p &lt; 0.05), and remained significantly elevated through D56, albeit a declining trend. Compared to GFR of sham mice (100%), the GFR of RKM mice gradually increased to 36% at D3, 43% at D7 and 69% at D14. By D21 post surgery, the GFR of RKM mice rose to 71% of sham (800 ± 106 vs 1121 ± 47 μL/min/100 g, p &gt; 0.05) and plateaued through day 28 (69% of sham), suggesting that the early rise in AP and impaired autoregulation may have caused GHF in the RKM mice. The adaptive increase in GFR post RKM surgery was associated with a trend towards increased renal leukocytes, monocyte/macrophages, CD3 T cells and CD4/CD8 subsets at D14 and significantly elevated albuminuria at D28 (832 ± 227 vs 341 ± 15 μg/day, p &lt; 0.05), implying hyperfiltration-induced renal inflammation and glomerular damage. Importantly, the GFR declined to 57% of sham levels by day 56 (597 ± 86 vs 1047 ± 80 μL/min/100 g, p &lt; 0.05), suggesting progressive glomerular injury. We conclude that impaired autoregulation exposes the kidney to both inflammation and GHF, causing glomerular injury, albuminuria, and CKD progression. This work is supported by a NIDDK K01 DK126792 and a University of Rochester Environmental Health Science Center Pilot award (as part of a NIEHS P30ES001247) to JW. 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.

Diaschisis Profiles in the Cerebellar Response to Hemodynamic Stimuli: Insights From Dynamic Measurement of Cerebrovascular Reactivity to Identify Occult and Transient Maxima.

Crossed cerebellar diaschisis (CCD) refers to depressions in perfusion and metabolism within the cerebellar hemisphere contralateral to supratentorial disease. Prior investigation into CCD in cerebrovascular reactivity (CVR) has been limited to terminal CVR estimations (CVRend ). We recently have demonstrated the presence of unsustained CVR maxima (CVRmax ) using dynamic CVR analysis, offering a fully dynamic characterization of CVR to hemodynamic stimuli. To investigate CCD in CVRmax from dynamic blood oxygen level-dependent (BOLD) MRI, by comparison with conventional CVRend estimation. Retrospective. A total of 23 patients (median age: 51 years, 10 females) with unilateral chronic steno-occlusive cerebrovascular disease, without prior knowledge of CCD status. A 3-T, T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) and acetazolamide-augmented BOLD imaging performed with a gradient-echo echo-planar imaging (EPI) sequence. A custom denoising pipeline was used to generate BOLD-CVR time signals. CVRend was established using the last minute of the BOLD response relative to the first-minute baseline. Following classification of healthy versus diseased cerebral hemispheres, CVRmax and CVRend were calculated for bilateral cerebral and cerebellar hemispheres. Three independent observers evaluated all data for the presence of CCD. Pearson correlations for comparing CVR across hemispheres, two-proportion Z-tests for comparing CCD prevalence, and Wilcoxon signed-rank tests for comparing median CVR. The level of statistical significance was set at P≤ 0.05. CCD-related changes were observed on both CVRend and CVRmax maps, with all CCD+ cases identifiable by inspection of either map. Diseased cerebral and contralateral cerebellar hemispheric CVR correlations in CCD+ patients were stronger when using CVRend (r=0.728) as compared to CVRmax (r=0.676). CVR correlations between healthy cerebral hemispheres and contralateral cerebellar hemispheres were stronger for CVRmax (r=0.739) than for CVRend (r=0.705). CCD-related alterations could be observed in CVR examinations. Conventional CVRend may underestimate CVR and could exaggerate CCD. 4. Stage 3.

Simulation of Angiogenesis in Three Dimensions: Development of the Retinal Circulation

A theoretical model is used to describe the three-dimensional development of the retinal circulation in the human eye, which occurs after the initial spread of vasculature across the inner surface of the retina. In the model, random sprouting angiogenesis is driven by a growth factor that is produced in tissue at a rate dependent on oxygen level and diffuses to existing vessels. Vessel sprouts connect to form pathways for blood flow and undergo remodeling and pruning. These processes are controlled by known or hypothesized vascular responses to hemodynamic and biochemical stimuli, including conducted responses along vessel walls. The model shows regression of arterio-venous connections on the surface of the retina, allowing perfusion of the underlying tissue. A striking feature of the retinal circulation is the formation of two vascular plexuses located at the inner and outer surfaces of the inner nuclear layer within the retina. The model is used to test hypotheses regarding the formation of these structures. A mechanism based on local production and diffusion of growth factor is shown to be ineffective. However, sprout guidance by localized structures on the boundaries of the inner nuclear layer can account for plexus formation. The resulting networks have vascular density, perfusion and oxygen transport characteristics consistent with observed properties. The model shows how stochastic generation of vascular sprouts combined with a set of biologically based response mechanisms can lead to the generation of a specialized three-dimensional vascular structure with a high degree of organization.

Acute regulation of erythropoietin via lower body negative pressure: Influence of sex and age.

The regulation of erythropoiesis via hemodynamic stimuli such as reduced central blood volume (CBV) remains uncertain in women and elderly individuals. This study assessed the acute effects of lower body negative pressure (LBNP) on key endocrine biomarkers regulating erythropoiesis, that is, erythropoietin (EPO) and copeptin, in young and older women and men (n= 87). Transthoracic echocardiography and hemodynamics were assessed throughout incremental LBNP levels for 1hour, or until presyncope, with established methods. Venous blood samples were collected at baseline and immediately after termination of the orthostatic tolerance (OT) test for subsequent hormone analyses. The average age of young women and men (33.1± 6.0 vs. 29.5± 6.9yr) and older women and men (63.8± 8.0 vs. 65.3± 8.9yr) as well as their physical activity levels were matched within each age and sex group. CBV, as determined by right atrial volume, was reduced in all individuals at the end of the OT test (p< 0.001). The average OT time ranged from 50.1 to 58.1min in all individuals. LBNP increased circulating EPO in young women (p= 0.023) but not in young men or older individuals. Copeptin was increased in all individuals with LBNP but was exclusively associated with EPO in men (r= 0.39, p= 0.013). The present study indicates that the acute hemodynamic regulation of EPO production is both sex- and age-dependent.

In vivo vascularized scaffold with different shear-exposed models for lymphatic tissue regeneration

Current clinical treatments on lymphedema provide promising results, but also result in donor site morbidities. The establishment of a microenvironment optimized for lymphangiogenesis can be an alternative way to enhance lymphatic tissue formation. Hemodynamic flow stimuli have been confirmed to have an influential effect on angiogenesis in tissue engineering, but not on lymphatic vessel formation. Here, the three in vivo scaffolds generated from different blood stimuli in the subcutaneous layer, in the flow through pedicle, and in an arterio-venous (AV) loop model, were created to investigate potential of lymphangiogenesis of scaffolds containing lymphatic endothelial cells (LECs). Our results indicated that AV loop model displayed better lymphangiogenesis in comparison to the other two models with slower flow or no stimuli. Other than hemodynamic force, the supplement of LECs is required for lymphatic vessel regeneration. The in vivo scaffold generated from AV loop model provides an effective approach for engineering lymphatic tissue in the clinical treatment of lymphedema.

GSDMD (Gasdermin D) Mediates Pathological Cardiac Hypertrophy and Generates a Feed-Forward Amplification Cascade via Mitochondria-STING (Stimulator of Interferon Genes) Axis

Cardiac hypertrophy is initially an adaptive response of cardiomyocytes to neurohumoral or hemodynamic stimuli. Evidence indicates that Ang II (angiotensin II) or pressure overload causes GSDMD (gasdermin D) activation in cardiomyocytes and myocardial tissues. However, the direct impact of GSDMD on cardiac hypertrophy and its underlying mechanisms are not fully understood. In this study, we examined the aberrant activation of GSDMD in mouse and human hypertrophic myocardia, and the results showed that GSDMD deficiency reduced Ang II or pressure overload-induced cardiac hypertrophy, dysfunction, and associated cardiomyocyte pyroptosis in mice. Mechanistically, Ang II-mediated GSDMD cleavage caused mitochondrial dysfunction upstream of STING (stimulator of interferon genes) activation in vivo and in vitro. Activation of STING, in turn, potentiated GSDMD-mediated cardiac hypertrophy. Moreover, deficiency of both GSDMD and STING suppressed cardiac hypertrophy in cardiac-specific GSDMD-overexpressing mice. Based on these findings, we propose a mechanism by which GSDMD generates a self-amplifying, positive feed-forward loop with the mitochondria-STING axis. This finding points to the prospects of GSDMD as a key therapeutic target for hypertrophy-associated heart diseases.

Valve Endothelial Cell Exposure to High Levels of Flow Oscillations Exacerbates Valve Interstitial Cell Calcification.

The aortic valve facilitates unidirectional blood flow to the systemic circulation between the left cardiac ventricle and the aorta. The valve’s biomechanical function relies on thin leaflets to adequately open and close over the cardiac cycle. A monolayer of valve endothelial cells (VECs) resides on the outer surface of the aortic valve leaflet. Deeper within the leaflet are sublayers of valve interstitial cells (VICs). Valve tissue remodeling involves paracrine signaling between VECs and VICs. Aortic valve calcification can result from abnormal paracrine communication between these two cell types. VECs are known to respond to hemodynamic stimuli, and, specifically, flow abnormalities can induce VEC dysfunction. This dysfunction can subsequently change the phenotype of VICs, leading to aortic valve calcification. However, the relation between VEC-exposed flow oscillations under pulsatile flow to the progression of aortic valve calcification by VICs remains unknown. In this study, we quantified the level of flow oscillations that VECs were exposed to under dynamic culture and then immersed VICs in VEC-conditioned media. We found that VIC-induced calcification was augmented under maximum flow oscillations, wherein the flow was fully forward for half the cardiac cycle period and fully reversed for the other half. We were able to computationally correlate this finding to specific regions of the aortic valve that experience relatively high flow oscillations and that have been shown to be associated with severe calcified deposits. These findings establish a basis for future investigations on engineering calcified human valve tissues and its potential for therapeutic discovery of aortic valve calcification.

Marked improvements in cardiac function in postmenopausal women exposed to blood withdrawal plus endurance training

ABSTRACT The cardiac phenotype of a substantial fraction of the population, i.e., mature women, is mainly unresponsive to endurance training (ET), the most effective intervention to improve cardiorespiratory fitness. This study assessed whether a novel intervention comprising additional haemodynamic stimuli may overcome the generalized limitations to modify the cardiac phenotype of middle-aged and older women. Fifteen healthy postmenopausal women (52–75 yr) were recruited. Transthoracic echocardiography and central haemodynamics were assessed during incremental cycle ergometry (i) in baseline conditions, (ii) after standard (10%) blood withdrawal and (iii) subsequent 8-week ET. Main outcomes such as left ventricular (LV) function and structure and blood volume (BV) were determined. Phlebotomy induced a 0.5 ± 0.1 l reduction of BV, which was re-established after ET. Decrements in LV end-systolic volume (−27%) and increments in LV ejection fraction (+8%) during exercise as well as improved E/A ratio were detected after ET compared with baseline. In parallel, ET induced a 10% increment in LV mass without a concomitant increase in LV size. In conclusion, postmenopausal women exhibit large improvements in cardiac systolic and diastolic functions along with LV concentric remodelling in response to the sequenced combination of blood withdrawal and ET.

Endothelial Inwardly Rectifying K+ Channel Subunit 2.1 Critically Enables Flow‐mediated Dilation in Cerebral Resistance Arteries

Cerebral blood flow is a highly regulated process tied to the expression of ion channels in endothelial and smooth muscle cells. Of particular note are endothelial inwardly rectifying K+ channels (KIR), membrane proteins that presumably sense hemodynamic stimuli such as blood flow. This study sought to clearly define the role of endothelial KIR2.1 in cerebral arterial blood flow sensing using floxed control and endothelial KIR2.1‐/‐ mice. Experiments progressed from single cell (patch‐clamp electrophysiology of cerebral endothelial and smooth muscle), to isolated vessel (myography of cerebral resistance arteries) and finally to intact organism (arterial spin‐labeling magnetic resonance imaging). Electrophysiological analysis confirmed the presence of KIR activity in endothelial cells from floxed but not endothelial KIR2.1‐/‐ mice; the former was subsequently shown to be flow sensitive. Smooth muscle KIR activity was comparable among the two animal groups. Vessel experiments next revealed that flow‐induced vasodilation was diminished in endothelial KIR2.1‐/‐ mice. In the absence of endothelium, Ba2+‐induced constriction was comparable among the two groups consistent with preserved smooth muscle KIR activity. Intriguingly, the diminishment of cellular and tissue level responses in endothelial KIR2.1‐/‐ mice did not lead to apparent cerebral flow abnormalities (cortex, cerebral nuclei, hippocampus, thalamus, hypothalamus and midbrain), at baseline or following a systemic blood pressure challenge (intraperitoneal phenylephrine). These findings underscore a role for endothelial KIR2.1 activity in hemodynamic sensing, one that is subtle and dynamically balanced with other mechanisms that set cerebral arterial blood flow.

Mechanisms and Clinical Implications of Endothelial Dysfunction in Arterial Hypertension.

The endothelium is composed of a monolayer of endothelial cells, lining the interior surface of blood and lymphatic vessels. Endothelial cells display important homeostatic functions, since they are able to respond to humoral and hemodynamic stimuli. Thus, endothelial dysfunction has been proposed as a key and early pathogenic mechanism in many clinical conditions. Given the relevant repercussions on cardiovascular risk, the complex interplay between endothelial dysfunction and systemic arterial hypertension has been a matter of study in recent years. Numerous articles have been published on this issue, all of which contribute to providing an interesting insight into the molecular mechanisms of endothelial dysfunction in arterial hypertension and its role as a biomarker of inflammation, oxidative stress, and vascular disease. The prognostic and therapeutic implications of endothelial dysfunction have also been analyzed in this clinical setting, with interesting new findings and potential applications in clinical practice and future research. The aim of this review is to summarize the pathophysiology of the relationship between endothelial dysfunction and systemic arterial hypertension, with a focus on the personalized pharmacological and rehabilitation strategies targeting endothelial dysfunction while treating hypertension and cardiovascular comorbidities.

Wall Shear Stress Topological Skeleton Variability Predicts Myocardial Infarction

Objective: Coronary atherosclerotic plaques experience a variety of haemodynamic stimuli linked to plaque progression and destabilisation that increases the risk of occlusion.1 Peculiar wall shear stress (WSS) features obtained from patient specific computational fluid dynamics (CFD) simulations have been associated with myocardial infarction (MI).2 Therefore, WSS based quantities may prove to have predictive capability for MI, allowing identification of lesions prone to rupture and improving the medical management of patients with coronary artery disease (CAD).

Computational Characterization of Mechanical, Hemodynamic, and Surface Interaction Conditions: Role of Protein Adsorption on the Regenerative Response of TEVGs.

Currently available small diameter vascular grafts (<6 mm) present several long-term limitations, which has prevented their full clinical implementation. Computational modeling and simulation emerge as tools to study and optimize the rational design of small diameter tissue engineered vascular grafts (TEVG). This study aims to model the correlation between mechanical-hemodynamic-biochemical variables on protein adsorption over TEVG and their regenerative potential. To understand mechanical-hemodynamic variables, two-way Fluid-Structure Interaction (FSI) computational models of novel TEVGs were developed in ANSYS Fluent 2019R3® and ANSYS Transient Structural® software. Experimental pulsatile pressure was included as an UDF into the models. TEVG mechanical properties were obtained from tensile strength tests, under the ISO7198:2016, for novel TEVGs. Subsequently, a kinetic model, linked to previously obtained velocity profiles, of the protein-surface interaction between albumin and fibrinogen, and the intima layer of the TEVGs, was implemented in COMSOL Multiphysics 5.3®. TEVG wall properties appear critical to understand flow and protein adsorption under hemodynamic stimuli. In addition, the kinetic model under flow conditions revealed that size and concentration are the main parameters to trigger protein adsorption on TEVGs. The computational models provide a robust platform to study multiparametrically the performance of TEVGs in terms of protein adsorption and their regenerative potential.