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Journal of Clinical Medicine Oct 2023Critical illness is often accompanied by a hemodynamic imbalance between macrocirculation and microcirculation, as well as mitochondrial dysfunction. Microcirculatory... (Review)
Review
Critical illness is often accompanied by a hemodynamic imbalance between macrocirculation and microcirculation, as well as mitochondrial dysfunction. Microcirculatory disorders lead to abnormalities in the supply of oxygen to tissue cells, while mitochondrial dysfunction leads to abnormal energy metabolism and impaired tissue oxygen utilization, making these conditions important pathogenic factors of critical illness. At the same time, there is a close relationship between the microcirculation and mitochondria. We introduce here the concept of a "critical unit", with two core components: microcirculation, which mainly comprises the microvascular network and endothelial cells, especially the endothelial glycocalyx; and mitochondria, which are mainly involved in energy metabolism but perform other non-negligible functions. This review also introduces several techniques and devices that can be utilized for the real-time synchronous monitoring of the microcirculation and mitochondria, and thus critical unit monitoring. Finally, we put forward the concepts and strategies of critical unit-guided treatment.
PubMed: 37892591
DOI: 10.3390/jcm12206453 -
The Journal of Clinical Investigation Oct 2023Type 2 diabetes mellitus (T2DM), characterized by hyperglycemia and dyslipidemia, leads to nonproliferative diabetic retinopathy (NPDR). NPDR is associated with...
Type 2 diabetes mellitus (T2DM), characterized by hyperglycemia and dyslipidemia, leads to nonproliferative diabetic retinopathy (NPDR). NPDR is associated with blood-retina barrier disruption, plasma exudates, microvascular degeneration, elevated inflammatory cytokine levels, and monocyte (Mo) infiltration. Whether and how the diabetes-associated changes in plasma lipid and carbohydrate levels modify Mo differentiation remains unknown. Here, we show that mononuclear phagocytes (MPs) in areas of vascular leakage in DR donor retinas expressed perilipin 2 (PLIN2), a marker of intracellular lipid load. Strong upregulation of PLIN2 was also observed when healthy donor Mos were treated with plasma from patients with T2DM or with palmitate concentrations typical of those found in T2DM plasma, but not under high-glucose conditions. PLIN2 expression correlated with the expression of other key genes involved in lipid metabolism (ACADVL, PDK4) and the DR biomarkers ANGPTL4 and CXCL8. Mechanistically, we show that lipid-exposed MPs induced capillary degeneration in ex vivo explants that was inhibited by pharmaceutical inhibition of PPARγ signaling. Our study reveals a mechanism linking dyslipidemia-induced MP polarization to the increased inflammatory cytokine levels and microvascular degeneration that characterize NPDR. This study provides comprehensive insights into the glycemia-independent activation of Mos in T2DM and identifies MP PPARγ as a target for inhibition of lipid-activated MPs in DR.
Topics: Humans; Cytokines; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Dyslipidemias; Lipids; Macrophages; Perilipin-2; PPAR gamma; Retina
PubMed: 37781924
DOI: 10.1172/JCI161348 -
EXCLI Journal 2023As a significant non-communicable disease, cardiovascular disease is the leading cause of death for both men and women, comprises almost twenty percent of deaths in most... (Review)
Review
As a significant non-communicable disease, cardiovascular disease is the leading cause of death for both men and women, comprises almost twenty percent of deaths in most racial and ethnic groups, can affect greater than twenty-five million individuals worldwide over the age of twenty, and impacts global economies with far-reaching financial challenges. Multiple factors can affect the onset of cardiovascular disease that include high serum cholesterol levels, elevated blood pressure, tobacco consumption and secondhand smoke exposure, poor nutrition, physical inactivity, obesity, and concurrent diabetes mellitus. Yet, addressing any of these factors cannot completely eliminate the onset or progression of cardiovascular disorders. Novel strategies are necessary to target underlying cardiovascular disease mechanisms. The silent mating type information regulation 2 homolog 1 ) (SIRT1), a histone deacetylase, can limit cardiovascular injury, assist with stem cell development, oversee metabolic homeostasis through nicotinamide adenine dinucleotide (NAD) pathways, foster trophic factor protection, and control cell senescence through the modulation of telomere function. Intimately tied to SIRT1 pathways are mammalian forkhead transcription factors (FoxOs) which can modulate cardiac disease to reduce oxidative stress, repair microcirculation disturbances, and reduce atherogenesis through pathways of autophagy, apoptosis, and ferroptosis. AMP activated protein kinase (AMPK) also is critical among these pathways for the oversight of cardiac cellular metabolism, insulin sensitivity, mitochondrial function, inflammation, and the susceptibility to viral infections such as severe acute respiratory syndrome coronavirus that can impact cardiovascular disease. Yet, the relationship among these pathways is both intricate and complex and requires detailed insight to successfully translate these pathways into clinical care for cardiovascular disorders.
PubMed: 37593239
DOI: 10.17179/excli2023-6306 -
Animal Models and Experimental Medicine Aug 2023Pericytes are the main cellular components of tiny arteries and capillaries. Studies have found that pericytes can undergo morphological contraction or relaxation under... (Review)
Review
Pericytes are the main cellular components of tiny arteries and capillaries. Studies have found that pericytes can undergo morphological contraction or relaxation under stimulation by cytokines, thus affecting the contraction and relaxation of microvessels and playing an essential role in regulating vascular microcirculation. Moreover, due to the characteristics of stem cells, pericytes can differentiate into a variety of inflammatory cell phenotypes, which then affect the immune function. Additionally, pericytes can also participate in angiogenesis and wound healing by interacting with endothelial cells in vascular microcirculation disorders. Here we review the origin, biological phenotype and function of pericytes, and discuss the potential mechanisms of pericytes in vascular microcirculation disorders, especially in pulmonary hypertension, so as to provide a sound basis and direction for the prevention and treatment of vascular microcirculation diseases.
Topics: Pericytes; Microcirculation; Endothelial Cells; Capillaries; Biology
PubMed: 37317664
DOI: 10.1002/ame2.12334 -
Frontiers in Endocrinology 2023Diabetic nephropathy (DN) is one of the most common complications of diabetes, and its main manifestations are progressive proteinuria and abnormal renal function, which... (Review)
Review
Diabetic nephropathy (DN) is one of the most common complications of diabetes, and its main manifestations are progressive proteinuria and abnormal renal function, which eventually develops end stage renal disease (ESRD). The pathogenesis of DN is complex and involves many signaling pathways and molecules, including metabolic disorders, genetic factors, oxidative stress, inflammation, and microcirculatory abnormalities strategies. With the development of medical experimental techniques, such as single-cell transcriptome sequencing and single-cell proteomics, the pathological alterations caused by kidney cell interactions have attracted more and more attention. Here, we reviewed the characteristics and related mechanisms of crosstalk among kidney cells podocytes, endothelial cells, mesangial cells, pericytes, and immune cells during the development and progression of DN and highlighted its potential therapeutic effects.
Topics: Humans; Diabetic Nephropathies; Endothelial Cells; Microcirculation; Kidney; Mesangial Cells; Diabetes Mellitus
PubMed: 37538798
DOI: 10.3389/fendo.2023.1173933 -
Journal of Cardiothoracic and Vascular... Oct 2023Cardiogenic shock causes hypoperfusion within the microcirculation, leading to impaired oxygen delivery, cell death, and progression of multiple organ failure.... (Review)
Review
Cardiogenic shock causes hypoperfusion within the microcirculation, leading to impaired oxygen delivery, cell death, and progression of multiple organ failure. Mechanical circulatory support (MCS) is the last line of treatment for cardiac failure. The goal of MCS is to ensure end-organ perfusion by maintaining perfusion pressure and total blood flow. However, machine-blood interactions and the nonobvious translation of global macrohemodynamics into the microcirculation suggest that the use of MCS may not necessarily be associated with improved capillary flow. With the use of hand-held vital microscopes, it is possible to assess the microcirculation at the bedside. The paucity of literature on the use of microcirculatory assessment suggests the need for an in-depth look into microcirculatory assessment within the context of MCS. The purpose of this review is to discuss the possible interactions between MCS and microcirculation, as well as to describe the research conducted in this area. Regarding sublingual microcirculation, 3 types of MCS will be discussed: venoarterial extracorporeal membrane oxygenation, intra-aortic balloon counterpulsation, and microaxial flow pumps (Impella).
Topics: Humans; Microcirculation; Mouth Floor; Shock, Cardiogenic; Heart Failure; Hemodynamics; Heart-Assist Devices; Intra-Aortic Balloon Pumping
PubMed: 37330330
DOI: 10.1053/j.jvca.2023.05.028 -
Frontiers in Pediatrics 2023Cardiovascular instability and reduced oxygenation are regular perioperative critical events associated with anesthesia requiring intervention in neonates and young... (Review)
Review
Cardiovascular instability and reduced oxygenation are regular perioperative critical events associated with anesthesia requiring intervention in neonates and young infants. This review article addresses the current modalities of assessing this population's adequate end-organ perfusion in the perioperative period. Assuring adequate tissue oxygenation in critically ill infants is based on parameters that measure acceptable macrocirculatory hemodynamic parameters such as vital signs (mean arterial blood pressure, heart rate, urinary output) and chemical parameters (lactic acidosis, mixed venous oxygen saturation, base deficit). Microcirculation assessment represents a promising candidate for assessing and improving hemodynamic management strategies in perioperative and critically ill populations. Evaluation of the functional state of the microcirculation can parallel improvement in tissue perfusion, a term coined as "hemodynamic coherence". Less information is available to assess microcirculatory disturbances related to higher mortality risk in critically ill adults and pediatric patients with septic shock. Techniques for measuring microcirculation have substantially improved in the past decade and have evolved from methods that are limited in scope, such as velocity-based laser Doppler and near-infrared spectroscopy, to handheld vital microscopy (HVM), also referred to as videomicroscopy. Available technologies to assess microcirculation include sublingual incident dark field (IDF) and sublingual sidestream dark field (SDF) devices. This chapter addresses (1) the physiological basis of microcirculation and its relevance to the neonatal and pediatric populations, (2) the pathophysiology associated with altered microcirculation and endothelium, and (3) the current literature reviewing modalities to detect and quantify the presence of microcirculatory alterations.
PubMed: 37842022
DOI: 10.3389/fped.2023.1123405 -
Medicinski Glasnik : Official... Aug 2023Aim To investigate the effect of direct epineural electrical stimulation of the nerve on the nature of reparative processes in the bone stump. Methods Three series of...
Aim To investigate the effect of direct epineural electrical stimulation of the nerve on the nature of reparative processes in the bone stump. Methods Three series of experiments were carried out with amputation of the thigh in the middle third and muscle plasty. In the 1st and 2nd experimental series a perineural catheter was brought to the stump of the sciatic nerve, through which mechanical irritation of the nerve was performed for 20 days daily for 20 minutes. In the 2nd series, an electrode was added to the nerve and epineural electrical stimulation was performed daily for 20 days. Animals of the 3rd series served as control. The observation periods were 1, 3, 6 months. Histological research method with filling vessels with ink-gelatin mixture was applied. Results In the 1st series, there was a sharp distortion of the reparative process, which consisted of a violation of microcirculation, changes in shape, resorption of the cortical diaphyseal plate, fractures, deformations. In most experiments of the 2nd series, organotypic stumps were formed with normalization of microcirculation. In the 3rd series, results of the formation of the stump were better than in the 1st, but worse than in the 2nd series. Conclusions Painful nerve irritation after amputation leads to a significant disturbance of microcirculation and reparative regeneration at the end of the bone stump with the development of pathological restructuring of bone tissue. Electrostimulation of the nerve improves microcirculation and reparative regeneration of the bone tissue.
PubMed: 37421178
DOI: 10.17392/1602-23 -
Clinical Ophthalmology (Auckland, N.Z.) 2023Lattice degeneration (LD), routinely diagnosed with indirect ophthalmoscopy, is one of the most common and clinically significant peripheral retinal findings. In this... (Review)
Review
Lattice degeneration (LD), routinely diagnosed with indirect ophthalmoscopy, is one of the most common and clinically significant peripheral retinal findings. In this review, we have summarized the data on currently available imaging techniques which help to improve diagnosis and our understanding of LD pathogenesis. Ultra-wide field imaging provides reliable color fundus capturing for the primary diagnosis of LD and may also be used as a screening tool. Wide-field imaging can be used for targeted documentation of LD lesions using true colors and with minimal optical distortions. Information on the status of the vitreoretinal interface, including detection of retinal holes, detachments, and vitreous tractions, can be obtained with peripheral structural optical coherence tomography (OCT) or scanning laser ophthalmoscopy in retro-mode. These techniques clarify the associated risks of rhegmatogenous retinal detachment. Fundus autofluorescence can provide details on atrophic changes. However, the risk of retinal detachment by means of this technique requires further investigation. OCT angiography may be successfully performed for some lesions. Taken together, OCT and OCT angiography demonstrate thinning of the choroid, alteration of local choroidal microcirculation, and, in severe lesions, involvement of the sclera. OCT angiography confirms loss of retinal microcirculation within LD lesion, which was previously shown with fluorescein angiography. In conclusion, despite relatively simple primary diagnosis, imaging of LD lesions remains challenging due to their peripheral localization. However, several new strategies, including ultra-wide field imaging, peripheral OCT, and scanning laser ophthalmoscopy, make LD imaging possible on a routine basis, improving diagnosis and understanding of LD pathogenesis.
PubMed: 37605766
DOI: 10.2147/OPTH.S405200 -
Biomedicine & Pharmacotherapy =... Aug 2023Coronary microvascular dysfunction (CMD) is a high-risk factor for a variety of cardiovascular events. Due to its complex aetiology and concealability, knowledge of the... (Review)
Review
Coronary microvascular dysfunction (CMD) is a high-risk factor for a variety of cardiovascular events. Due to its complex aetiology and concealability, knowledge of the pathophysiological mechanism of CMD is still limited at present, which greatly restricts its clinical diagnosis and treatment. Studies have shown that CMD is closely related to a variety of cardiovascular diseases, can aggravate the occurrence and development of cardiovascular diseases, and is closely related to a poor prognosis in patients with cardiovascular diseases. Improving coronary microvascular remodelling and increasing myocardial perfusion might be promising strategies for the treatment of cardiovascular diseases. In this paper, the pathogenesis and functional assessment of CMD are reviewed first, along with the relationship of CMD with cardiovascular diseases. Then, the latest strategies for the treatment of CMD and cardiovascular diseases are summarized. Finally, urgent scientific problems in CMD and cardiovascular diseases are highlighted and future research directions are proposed to provide prospective insights for the prevention and treatment of CMD and cardiovascular diseases in the future.
Topics: Humans; Cardiovascular Diseases; Coronary Circulation; Myocardial Ischemia; Microcirculation
PubMed: 37321056
DOI: 10.1016/j.biopha.2023.115011