Pathological vascular remodeling of the vessel wall refers to the structural and functional changes of the vessel wall that occur in response to injury that eventually leads to cardiovascular disease. The vessel wall is composed of two main types of cells, endothelial cells and vascular smooth muscle cells, whose communication is crucial in both the development of the vasculature and the homeostasis of mature vessels. Changes in the dialogue between endothelial cells and vascular smooth muscle cells are associated with various pathological states that triggers remodeling of the vascular wall. For many years, considerable efforts have been made to develop effective diagnoses and treatments for these pathologies by studying their mechanisms in both in vitro and in vivo models. Compared to animal models, in vitro models can provide great opportunities to obtain data in a more homogeneous, economical and massive way, providing an overview of the signaling pathways responsible for these pathologies. The implementation of three-dimensional in vitro co-culture models for the study of other pathologies has been postulated as a potentially applicable methodology, which determines the importance of its application in studies of cardiovascular diseases. In this article we present a method for culturing human endothelial cells and vascular smooth muscle cells, grown under non-adherent conditions, that generate three-dimensional spheroidal structures with greater physiological equivalence to in vivo conditions. This in vitro modeling could be used as a study tool to identify cellular and molecular mechanisms involved in the pathological processes underlying vascular remodeling.

Sepsis and septic shock result from an inadequate host response to an infection, which causes organ dysfunction. The progression of this condition is manifested by the occurrence of successive clinical stages, resulting from the systemic inflammatory response secondary to the activation of different inflammatory mediators, leading to organ dysfunction. There is a high burden of evidence on the role of endotoxin in the pathogenesis of sepsis and its crucial role in triggering the inflammatory response in sepsis caused by gram-negative bacteria. The coagulation cascade activation in sepsis patients is part of the host\'s adaptive immune response to infection. The endothelium is the main target in sepsis, which is metabolically active and can.

BACKGROUND: Lamellar keratoplasties have had a great impact in the management of corneal edema due to endothelial dysfunction. Minimally invasive transplant techniques such as Descemet Membrane Endothelial Keratoplasty (DMEK) have helped to reduce the morbidity involved in performing penetrating keratoplasty in this type of patient. Even so, these are complex techniques that are not free of complications and require a long line of surgical learning and an even more demanding experience in postoperative management.
METHODS: An 89-year-old woman suffering from Fuchs endothelial dystrophy and undergoing combined cataract and DMEK surgery presented stromal edema predominantly inferior and sectoral detachment of the graft 24 h after the intervention. After re-bubbling in consultations and 4 days later, the graft was observed rolled and free in the anterior chamber. She underwent re-DMEK with preservation of the original graft after 24 h, with de-epithelialization to optimize visualization. The graft was stained with trypan blue and the posterior stroma was protected with air. The graft was reimplanted under intraocular maneuvers and with an air bubble. 24 h after surgery, the adhered graft was observed, with a great decrease in stromal edema. One month later, the patient had a clear cornea, persistent complete graft adhesion, and visual acuity of 0.9.
CONCLUSIONS: The discovery of free roll in the anterior chamber after DMEK surgery constitutes the most complex form of graft detachment. Corneal edema as well as the arrangement of the different intraocular structures are conditions to be considered for the surgical resolution of this complication. In many cases, surgical repositioning of the graft is feasible, which means saving costs without the need to use new donor corneal tissues.

The objective of the present case is to describe a variation in the Preserflo Microshunt surgical technique, placing it in the posterior chamber to minimise the risk of endothelial cell loss in cases with a compromised endothelium. The patient was a 72-year-old pseudophakic woman, with granular dystrophy and a primary diagnosis of open-angle glaucoma presenting with a progressive visual field defect and an IOP of 26 mmHg with maximal medical therapy. The cornea had incipient stromal folds with an endothelial count of 700 cells/mm2. A Preserflo Microshunt was implanted in the posterior chamber to minimise the possibility of further damage to the corneal endothelium. Six months after surgery, the implant remains functional. The IOP is 9 mmHg without medications. As far as we know, this is the first Preserflo implanted in the posterior chamber described in the literature.

OBJECTIVE: NRP1 inflammasome is crucial in endothelial dysfunction. Platelets are mandatory for the inflammation that precedes it. Aspirin could inhibit NLRP1 inflammasome in endothelial cells, and clopidogrel could also provoke a reduction in vascular inflammation. A study was carried out on the influence of platelet inflammatory inhibition by P2Y receptor inhibition versus COX enzyme inhibition on the transcription of NLRP1 inflammasome in endothelial cells.
METHODS: An open-label, prospective, randomised crossover study with two periods of platelet inhibition enrolled 20 healthy volunteers. They received clopidogrel 75mg/day/7days and aspirin 100mg/day/7days. A venous blood sample was collected from all participants before and after this period. Human aortic endothelial cells (HAECs) were exposed for 2h in cultures. NLRP1 gene expression was then analysed in these cultures.
RESULTS: HAEC cultures that were exposed to baseline plasma showed higher expression of NLRP1 than HAECs exposed to plasma after one week of aspirin or clopidogrel intake [relative quantification (RQ), 1.077±0.05 vs. 1.002±0.06; OR, 1.8; 95% CI, 1.1-2.9; P<.01 and 1.077±0.05 vs. 1.04±0.03; OR, 1.7; 95% CI, 1.2-2.6; P<.001, respectively]. NLRP1 expression in HAEC cultures exposed to plasma after one week of aspirin or clopidogrel was similar to that observed in control HAECs that was no exposed to human plasma (PBS) [RQ; 1.002±0.06 vs. 1.009±0.03; OR, 0.9; 95% CI, 0.5-1.4; P=.7, and 1.04±0.03 vs. 1.009±0.03; OR, 0.8; 95% CI, 0.3-1.2; P=.5, respectively]. No difference was observed in NLRP1 percentage reduction in HAEC after aspirin or clopidogrel exposure (3.8% vs. 2.8%, P=.3, respectively).
CONCLUSIONS: Platelet inhibition by P2Y pathway is similar to COX pathway in NLRP1 expression inhibition in HAECs.

OBJECTIVE: To evaluate the effects and safety of topical drops of perfluorohexyloctane (F6H8) on the ocular surface and the corneal endothelium.
METHODS: Forty-five patients (90 eyes) diagnosed with dry eye disease were recruited and prescribed treatment with F6H8 as part of a six-month prospective multicentre study. Variables in corneal staining were documented using the National Eye Institute/Industry Workshop scale. The conjunctival variables included using the Oxford scale, as well as corneal parameters, such as central corneal thickness, cell density, coefficient of variation, hexagonality, and mean cell area, at the start of the study, and at 3months and 6months. Compliance and satisfaction with the treatment were measured.
RESULTS: F6H8 drops reduced mean corneal staining based on the NEI scale in compliant patients to a mean of -0.84 ± 1.95 at 3months (P=.001) and to -1.65 ± 2.42 at 6months (P<.001). Conjunctival staining at 6months showed a mean decrease of -0.13 (P=.319). The endothelial parameters did not show a significant difference, in contrast to the central corneal thickness that showed a statistically significant decrease (545.30 ± 32.25 at the start of the study to 538.40 ± 31.36 after 6months, P=.009). At the end of the study, 46% of patients reported feeling subjectively better, 40.5% felt the same, and 13.5% felt subjectively worse.
CONCLUSIONS: Topical treatment with F6H8 for dried eye disease did not alter the measured variables of the corneal endothelium, but showed improvement in corneal staining and satisfaction.

Increased blood pressure variability (BPV) is associated with higher cardiovascular risk. The association between BPV and fluid status in hypertensive patients has not been investigated so far. The aim of the present study was to determine the contribution of fluid balance to BPV and impact on endothelial and cardiac functions among primary hypertensive patients.
This is a prospective interventional study conducted in primary hypertensive patients with one-year follow-up. Volume status measurements by a body composition monitor, ambulatory blood pressure (BP) monitoring, echocardiographic and carotid intima-media thickness (CIMT) measurements were performed at enrollment and at twelfth. Patients in one of the two groups were kept negative hydrated during trial with diuretic treatment. Patients in other group were positively hydrated (hypervolemic) at enrollment, antihypertensive drugs other than diuretics (vasodilator agents) were added or intensified according to the BP monitoring. Average real variability (ARV) index was used for establishing the prognostic significance of BPV.
The study population consisted of 50 patients with a mean age of 54.5±8.8 years. At the end of one-year follow-up, patients in negative hydrated group were found to have significantly lower BP, CIMT, left ventricle mass index (LVMI) and systolic and diastolic ARV. More weight gain and higher systolic BP were major risk factors of high systolic ARV. Patients who have improvement in CIMT and LVMI were considered as target organ damage (TOD) recovery present. In negatively hydrated group, TOD significantly reduced during trial. In patients who have TOD recovery, BPV significantly more reduced like systolic and diastolic BP. Significant risk factors associated with the presence of TOD were 24h systolic BP and daytime and night time diastolic ARV and night time diastolic BP.
Addition of diuretic to established treatment or intensified diuretic treatment and keeping patients in negative hydration status resulted in reduction in BPV at twelfth month of follow-up. More weight gain and higher systolic BP are major risk factors of high systolic ARV, but not hypervolemia. BPV, especially diastolic ARV, was significantly associated with TOD.

The physiological regulation of vascular function is essential for cardiovascular health and depends on adequate control of molecular mechanisms triggered by endothelial cells in response to mechanical and chemical stimuli induced by blood flow. Endothelial dysfunction is one of the major risk factors for cardiovascular disease, where an imbalance between synthesis of vasodilator and vasoconstrictor molecules is one of its main mechanisms. In this context, the shear stress is one of the most important mechanical stimuli to improve vascular function, due to endothelial mechanotransduction, triggered by stimulation of various endothelial mechanosensors, induce signaling pathways culminating in increased bioavailability of vasodilators molecules such as nitric oxide, that finally trigger the angiogenic mechanisms. These mechanisms allow providing the physiological basis for the effects of exercise on vascular health. In this review it is discussed the molecular mechanisms involved in the vascular response induced by shear stress and its impact in reversing vascular injury associated with the most prevalent cardiovascular disease in our population.

The omentin is an adipokine, which role is due to the capacity of regulate metabolic (insulin sensitivity) and anti-inflammatory activities, thus conferring vascular protection during obesity and diabetes mellitus type 2. By this, it is important to know the mechanisms by which omentin confers cardiovascular protection, with the purpose of establish omentin a possible therapeutic target or molecule on this scenario.

The prevalence of diabetes mellitus increased during the last century and it is estimated that 45% of the patients are not diagnosed. In South America the prevalence of diabetes and chronic kidney disease (CKD) increased, with a great disparity among the countries with respect to access to dialysis. In Ecuador it is one of the main causes of mortality, principally in the provinces located on the coast of the Pacific Ocean. The greatest single cause of beginning dialysis is diabetic nephropathy (DN). Even using the best therapeutic options for DN, the residual risk of proteinuria and of terminal CKD remains high. In this review we indicate the importance of the problem globally and in our region. We analyse relevant cellular and molecular studies that illustrate the crucial significance of glomerular events in DN development and evolution and in insulin resistance. We include basic anatomical, pathophysiological and clinical concepts, with special attention to the role of angiogenic factors such as the vascular endothelial growth factor (VEGF-A) and their relationship to the insulin receptor, endothelial isoform of nitric oxide synthase (eNOS) and angiopoietins. We also propose various pathways that have therapeutic potential in our opinion. Greater in-depth study of VEGF-A and angiopoietins, the state of glomerular VEGF resistance, the relationship of VEGF receptor 2/nephrin, VEGF/insulin receptors/nephrin and the relationship of VEGF/eNOS-NO at glomerular level could provide solutions to the pressing world problem of DN and generate new treatment alternatives.