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PloS One 2024Coronary microvascular dysfunction (CMD) is a critical pathogenesis of cardiovascular diseases. Lower endothelial nitric oxide synthase (eNOS) phosphorylation leads to...
Coronary microvascular dysfunction (CMD) is a critical pathogenesis of cardiovascular diseases. Lower endothelial nitric oxide synthase (eNOS) phosphorylation leads to reduced endothelium-derived relaxing factor nitric oxide (NO) generation, causing and accelerating CMD. Endoplasmic reticulum stress (ER stress) has been shown to reduce NO production in umbilical vein endothelial cells. Oxidized low-density lipoprotein (ox-LDL) damages endothelial cell function. However, the relationship between ox-LDL and coronary microcirculation has yet to be assessed. Short-chain fatty acid (SCFA), a fermentation product of the gut microbiome, could improve endothelial-dependent vasodilation in human adipose arterioles, but the effect of SCFA on coronary microcirculation is unclear. In this study, we found ox-LDL stimulated expression of ER chaperone GRP78. Further, we activated downstream PERK/eIF2a, IRE1/JNK, and ATF6 signaling pathways, decreasing eNOS phosphorylation and NO production in human cardiac microvascular endothelial. Furthermore, SCFA-propionate can inhibit ox-LDL-induced eNOS phosphorylation reduction and raise NO production; the mechanism is related to the inhibition of ER stress and downstream signaling pathways PERK/eIF2a, IRE1/JNK, and ATF6. In summary, we demonstrate that ox-LDL induced CMD by activating ER stress, propionate can effectively counteract the adverse effects of ox-LDL and protect coronary microcirculation function via inhibiting ER stress.
Topics: Humans; Endoplasmic Reticulum Stress; Lipoproteins, LDL; Nitric Oxide Synthase Type III; Endoplasmic Reticulum Chaperone BiP; Propionates; Nitric Oxide; Signal Transduction; Phosphorylation; Endothelial Cells; Coronary Vessels; Fatty Acids, Volatile; eIF-2 Kinase; Activating Transcription Factor 6; Microcirculation; Heat-Shock Proteins
PubMed: 38814895
DOI: 10.1371/journal.pone.0304551 -
Medical ozone alleviates acute lung injury by enhancing phagocytosis targeting NETs AMPK/SR-A1 axis.Journal of Biomedical Research May 2024Acute lung injury (ALI) linked to sepsis has a high mortality rate, with limited treatment options available. In recent studies, medical ozone has shown promising...
Acute lung injury (ALI) linked to sepsis has a high mortality rate, with limited treatment options available. In recent studies, medical ozone has shown promising results in alleviating inflammation and infection. Here, we aimed to evaluate the therapeutic potential of medical ozone in sepsis-induced ALI using a mouse model, measuring behavioral assessments, lung function, and blood flow. Western blot was used to quantify the levels of protein. In vitro, experiments on BMDM cells examine the impact of AMPK inhibitors and agonists on phagocytic activity. Results indicate that medical ozone can enhance the survival rate, ameliorate lung injury, and improve lung function and limb microcirculation in mice with ALI. Notably, it inhibits NETs formation, a crucial player in ALI development. Medical ozone also counteracts elevated TF, MMP-9, and IL-1β levels. In ALI mice, the effects of ozone are nullified and BMDMs exhibit impaired engulfment of NETs following knockout. Under normal physiological conditions, the use of an AMPK antagonist produces similar effects to knockout, significantly inhibiting the phagocytosis of NETs by BMDMs. On the contrary, AMPK agonists enhance this phagocytic process. In conclusion, medical ozone can alleviate sepsis-induced lung injury via the AMPK/SR-A1 pathway, thereby enhancing phagocytosis of NETs by macrophages.
PubMed: 38807426
DOI: 10.7555/JBR.38.20240038 -
Cardiovascular Diabetology May 2024Stress hyperglycemia, which is associated with poor prognosis in patients with acute myocardial infarction (AMI), can be determined using the stress hyperglycemia ratio...
Association of stress hyperglycemia ratio with left ventricular function and microvascular obstruction in patients with ST-segment elevation myocardial infarction: a 3.0 T cardiac magnetic resonance study.
BACKGROUND
Stress hyperglycemia, which is associated with poor prognosis in patients with acute myocardial infarction (AMI), can be determined using the stress hyperglycemia ratio (SHR). Impaired left ventricular function and microvascular obstruction (MVO) diagnosed using cardiac magnetic resonance (CMR) have also been proven to be linked to poor prognosis in patients with AMI and aid in risk stratification. However, there have been no studies on the correlation between fasting SHR and left ventricular function and MVO in patients with acute ST-segment elevation myocardial infarction (ASTEMI). Therefore, this study aimed to investigate the additive effect of fasting SHR on left ventricular function and global deformation in patients with ASTEMI and to explore the association between fasting SHR and MVO.
METHODS
Consecutive patients who underwent CMR at index admission (3-7 days) after primary percutaneous coronary intervention (PPCI) were enrolled in this study. Basic clinical, biochemical, and CMR data were obtained and compared among all patients grouped by fasting SHR tertiles: SHR1: SHR < 0.85; SHR2: 0.85 ≤ SHR < 1.01; and SHR3: SHR ≥ 1.01. Spearman's rho (r) was used to assess the relationship between fasting SHR and left ventricular function, myocardial strain, and the extent of MVO. Multivariable linear regression analysis was performed to evaluate the determinants of left ventricular function and myocardial strain impairment in all patients with AMI. Univariable and multivariable regression analyses were performed to investigate the correlation between fasting SHR and the presence and extent of MVO in patients with AMI and those with AMI and diabetes mellitus (DM).
RESULTS
A total of 357 patients with ASTEMI were enrolled in this study. Left ventricular ejection fraction (LVEF) and left ventricular global function index (LVGFI) were significantly lower in SHR2 and SHR3 than in SHR1. Compared with SHR1 and SHR2 groups, left ventricular strain was lower in SHR3, as evidenced by global radial (GRS), global circumferential (GCS), and global longitudinal (GLS) strains. Fasting SHR were negatively correlated with LVEF, LVGFI, and GRS (r = - 0.252; r = - 0.261; and r = - 0.245; all P<0.001) and positively correlated with GCS (r = 0.221) and GLS (r = 0.249; all P <0.001). Multivariable linear regression analysis showed that fasting SHR was an independent determinant of impaired LVEF, LVGFI, GRS, and GLS. Furthermore, multivariable regression analysis after adjusting for covariates signified that fasting SHR was associated with the presence and extent of MVO in patients with AMI and those with AMI and DM.
CONCLUSION
Fasting SHR in patients with ASTEMI successfully treated using PPCI is independently associated with impaired cardiac function and MVO. In patients with AMI and DM, fasting SHR is an independent determinant of the presence and extent of MVO.
Topics: Humans; Male; ST Elevation Myocardial Infarction; Middle Aged; Female; Ventricular Function, Left; Aged; Coronary Circulation; Blood Glucose; Hyperglycemia; Microcirculation; Predictive Value of Tests; Risk Factors; Ventricular Dysfunction, Left; Percutaneous Coronary Intervention; Biomarkers; Fasting; Magnetic Resonance Imaging, Cine; Prognosis; Magnetic Resonance Imaging; Time Factors
PubMed: 38802898
DOI: 10.1186/s12933-024-02271-6 -
Andes Pediatrica : Revista Chilena de... Apr 2024Sepsis is one of the main causes of admission to Intensive Care Units (ICU). The hemodynamic objectives usually sought during the resuscitation of the patient in septic... (Review)
Review
Sepsis is one of the main causes of admission to Intensive Care Units (ICU). The hemodynamic objectives usually sought during the resuscitation of the patient in septic shock correspond to macrohemodynamic parameters (heart rate, blood pressure, central venous pressure). However, persistent alterations in microcirculation, despite the restoration of macrohemodynamic parameters, can cause organ failure. This dissociation between the macrocirculation and microcirculation originates the need to evaluate organ tissue perfusion, the most commonly used being urinary output, lactatemia, central venous oxygen saturation (ScvO2), and veno-arterial pCO2 gap. Because peripheral tissues, such as the skin, are sensitive to disturbances in perfusion, noninvasive monitoring of peripheral circulation, such as skin temperature gradient, capillary refill time, mottling score, and peripheral perfusion index may be helpful as early markers of the existence of systemic hemodynamic alterations. Peripheral circulation monitoring techniques are relatively easy to interpret and can be used directly at the patient's bedside. This approach can be quickly applied in the intra- or extra-ICU setting. The objective of this narrative review is to analyze the various existing tissue perfusion markers and to update the evidence that allows guiding hemodynamic support in a more individualized therapy for each patient.
Topics: Humans; Child; Microcirculation; Hemodynamics; Shock, Septic; Monitoring, Physiologic; Hemodynamic Monitoring; Acute Disease; Sepsis; Biomarkers
PubMed: 38801369
DOI: 10.32641/andespediatr.v95i2.4915 -
Magnetic Resonance in Medical Sciences... May 2024We aimed to investigate the changes in intravoxel incoherent motion (IVIM) and diffusion parameters between in vivo and post-mortem conditions and the time dependency of...
PURPOSE
We aimed to investigate the changes in intravoxel incoherent motion (IVIM) and diffusion parameters between in vivo and post-mortem conditions and the time dependency of these parameters using two different mouse tumor models with different vessel lumen sizes.
METHODS
Six B16 and six MDA-MB-231 xenograft mice were scanned using 7 Tesla MRI under both in vivo/post-mortem conditions. Diffusion weighted imaging with 17 b-values (0-3000 s/mm) were obtained at two diffusion times (9 and 27.6 ms). The shifted apparent diffusion coefficient (sADC) using 2 b-values (200 and 1500 s/mm), non-Gaussian diffusion and IVIM parameters (ADC, K, f) were estimated at each of the diffusion times. The results were evaluated by repeated measures two-way analysis of variance and post hoc Bonferroni test.
RESULTS
In B16 tumors, f significantly decreased with post-mortem conditions (from 12.6 ± 6.5% to 5.2 ± 1.9%, P < 0.05 at long diffusion time; from 11.0 ± 2.4% to 4.6 ± 2.7%, P < 0.05 at short diffusion time). In MDA-MB-231 tumors, f also significantly decreased (from 8.8 ± 3.8% to 2.6 ± 1.1%, P < 0.05 at long; from 7.9 ± 5.4% to 2.9 ± 1.1%, P < 0.05 at short). No diffusion time dependency was observed (P = 0.59 in B16 and P = 0.77 in MDA-MB-231). The sADC and ADC values tended to decrease and the K value tended to increase after sacrificing and when increasing the diffusion time.
CONCLUSION
The f values dropped after sacrificing, confirming that IVIM MRI is a promising quantitative parameter to evaluate blood microcirculation. The presence of residual post-mortem f values suggested that the influence of water molecule diffusion in the blood lumen may contribute to the IVIM effect. Diffusion MRI parameter's time dependency and those changes after sacrificing could possibly provide additional insights into diffusion hindrance mechanisms.
PubMed: 38797683
DOI: 10.2463/mrms.mp.2023-0078 -
Laboratory Investigation; a Journal of... May 2024Addressing the existing gaps in our understanding of sex- and strain-dependent disparities in renal microhemodynamics, this study conducts an investigation into the...
Addressing the existing gaps in our understanding of sex- and strain-dependent disparities in renal microhemodynamics, this study conducts an investigation into the variations in renal function and related biological oscillators. Utilizing the genetically diverse mouse models BALB/c, C57BL/6, and KM, which serve as established proxies for the study of renal pathophysiology, we implemented laser Doppler flowmetry conjoined with wavelet transform analyses to interrogate the dynamic renal microcirculation. Creatinine, urea, uric acid, glucose, and cystatin C, were quantified to investigate potential divergences attributable to sex and genetic lineage. Our findings reveal marked sexual dimorphism in metabolite concentrations, as well as strain-specific variances, particularly in creatinine and cystatin C levels. Through the combination of Mantel tests and Pearson's correlation coefficients, we delineated the associations between renal functional metrics and microhemodynamics, uncovering interactions in female BALB/c mice for creatinine and uric acid, and in male C57BL/6 mice for cystatin C. Histopathological examination confirmed an augmented microvascular density in females and elucidating variations in the expression of estrogen receptor β amongst the strains. These data collectively highlight the influence of both sex and genetic constitution on renal microcirculation, providing an understanding that may inform the etiological exploration of renal ailments.
PubMed: 38797344
DOI: 10.1016/j.labinv.2024.102087 -
The Journal of Investigative Dermatology May 2024
PubMed: 38797323
DOI: 10.1016/j.jid.2024.04.019 -
Journal of Personalized Medicine May 2024Cardiovascular disease (CVD) is the most frequent cause of death worldwide. The alterations in the microcirculation may predict the cardiovascular mortality. The retinal... (Review)
Review
Cardiovascular disease (CVD) is the most frequent cause of death worldwide. The alterations in the microcirculation may predict the cardiovascular mortality. The retinal vasculature can be used as a model to study vascular alterations associated with cardiovascular disease. In order to quantify microvascular changes in a non-invasive way, fundus images can be taken and analysed. The central retinal arteriolar (CRAE), the venular (CRVE) diameter and the arteriolar-to-venular diameter ratio (AVR) can be used as biomarkers to predict the cardiovascular mortality. A narrower CRAE, wider CRVE and a lower AVR have been associated with increased cardiovascular events. Dynamic retinal vessel analysis (DRVA) allows the quantification of retinal changes using digital image sequences in response to visual stimulation with flicker light. This article is not just a review of the current literature, it also aims to discuss the methodological benefits and to identify research gaps. It highlights the potential use of microvascular biomarkers for screening and treatment monitoring of cardiovascular disease. Artificial intelligence (AI), such as Quantitative Analysis of Retinal vessel Topology and size (QUARTZ), and SIVA-deep learning system (SIVA-DLS), seems efficient in extracting information from fundus photographs and has the advantage of increasing diagnosis accuracy and improving patient care by complementing the role of physicians. Retinal vascular imaging using AI may help identify the cardiovascular risk, and is an important tool in primary cardiovascular disease prevention. Further research should explore the potential clinical application of retinal microvascular biomarkers, in order to assess systemic vascular health status, and to predict cardiovascular events.
PubMed: 38793083
DOI: 10.3390/jpm14050501 -
Medicina (Kaunas, Lithuania) Apr 2024The key objective in the hemodynamic treatment of septic shock is the optimization of tissue perfusion and oxygenation. This is usually achieved by the utilization of... (Review)
Review
The key objective in the hemodynamic treatment of septic shock is the optimization of tissue perfusion and oxygenation. This is usually achieved by the utilization of fluids, vasopressors, and inotropes. Dobutamine is the inotrope most commonly recommended and used for this purpose. Despite the fact that dobutamine was introduced almost half a century ago in the treatment of septic shock, and there is widespread use of the drug, several aspects of its pharmacodynamics remain poorly understood. In normal subjects, dobutamine increases contractility and lacks a direct effect on vascular tone. This results in augmented cardiac output and blood pressure, with reflex reduction in systemic vascular resistance. In septic shock, some experimental and clinical research suggest beneficial effects on systemic and regional perfusion. Nevertheless, other studies found heterogeneous and unpredictable effects with frequent side effects. In this narrative review, we discuss the pharmacodynamic characteristics of dobutamine and its physiologic actions in different settings, with special reference to septic shock. We discuss studies showing that dobutamine frequently induces tachycardia and vasodilation, without positive actions on contractility. Since untoward effects are often found and therapeutic benefits are occasional, its profile of efficacy and safety seems low. Therefore, we recommend that the use of dobutamine in septic shock should be cautious. Before a final decision about its prescription, efficacy, and tolerance should be evaluated throughout a short period with narrow monitoring of its wanted and side effects.
Topics: Humans; Cardiac Output; Cardiotonic Agents; Dobutamine; Hemodynamics; Shock, Septic; Animals
PubMed: 38792934
DOI: 10.3390/medicina60050751 -
Journal of Clinical Medicine May 2024This study aims to investigate the long-term effect of inactive systemic lupus erythematosus (SLE) on the retinal microcirculation measured via optical coherence...
This study aims to investigate the long-term effect of inactive systemic lupus erythematosus (SLE) on the retinal microcirculation measured via optical coherence tomography angiography (OCT-A). Twenty-four eyes of 24 patients with inactive SLE under hydroxychloroquine (HCQ) therapy were included. The OCT-A data (mainly vessel density (VD) and foveal avascular zone (FAZ) data of the superficial and of the deep capillary plexus (SCP, DCP) and the choriocapillaris (CC)) were analyzed and compared between the baseline examination (t) and 2 years later (t). At t, VD in the whole en face SCP and in the CC was notably reduced compared to t (SCP: = 0.001, CC: = 0.013). VD in the DCP, CRT and FAZ area showed no difference at t compared to t (DCP: = 0.128, FAZ: = 0.332, CRT fovea: = 0.296). Correlation analysis between the increase in cumulative doses of HCQ between t and t and the VD of the whole en face SCP did not show any correlation (Spearman r = 0.062 (95% CI -0.367; 0.477). SLE patients demonstrated a decrease in the retinal VD of the SCP and CC over a 2-year period. There was no correlation with the change in cumulative doses of HCQ. These results suggest an ongoing effect of the disease on the retinal and choriocapillary microcirculation.
PubMed: 38792521
DOI: 10.3390/jcm13102979