Fasudil

This study examined the therapeutic potential of a combination therapy using fasudil, a Rho-kinase inhibitor, and DETA NONOate (DN), a nitric oxide donor, delivered as a lipid admixture modified with a cyclic homing peptide known as CAR (CAR-lipid mixture) for the treatment of pulmonary arterial hypertension (PAH). CAR-lipid mixtures were initially prepared via a thin-film hydration method and then combined with fasudil, DN, or a mixture of both. The therapeutic efficacy of this drug-laden lipid mixture was evaluated in a Sugen/Hypoxia (Su/Hx) rat model of PAH by measuring RV systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), Fulton indices, and assessing right ventricular (RV) functions, as well as evaluating pulmonary vascular morphology...

BACKGROUND: Cerebral vasospasm (CVS) is one of the most critical factors associated with clinical outcomes of patients with subarachnoid hemorrhage (SAH). Clazosentan has been investigated worldwide as a prophylactic agent to prevent CVS. We evaluated a new CVS management protocol which included clazosentan. METHODS: Consecutive 138 patients with SAH, hospitalized in our institution between January 2017 and December 2022, were included in this study. Baseline characteristics, clinical findings, and operative records were analyzed retrospectively...

Objective: To explore the mechanism of osteoclast stimulatory transmembrane protein (OC-STAMP) overexpression on epithelial-mesenchymal transition (EMT) . Methods: In April 2021, mice alveolar type Ⅱ epithelial cells MLE-12 were divided into five groups: overexpression control group (NC group), Ocstamp overexpression group (over- Ocstamp group), Fasudil intervention group (over- Ocstamp +Fasudil group), silence control group (si-NC group), Ocstamp silence group (si- Ocstamp group). The protein expressions of OC-STAMP, epithelial marker protein-E-cadherin (E-cad), interstitial marker protein-α-smooth muscle actin (α-SMA), Ras homolog gene family member A (RhoA), Rho GDP dissociation inhibitor α (Rho GDIα), Rho-associated protein kinase (ROCK), phosphate myosin phosphatase (p-MYPT) were examined by Western blotting and Immunocytochemical staining...

Vascular remodeling is the pathogenic basis of hypertension and end organ injury, and the proliferation of vascular smooth muscle cells (VSMCs) is central to vascular remodeling. Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are key effectors of the Hippo pathway and crucial for controlling cell proliferation, apoptosis and differentiation. The present study investigated the role of YAP/TAZ in cardiac and vascular remodeling of angiotensin II-induced hypertension...

Small molecules such as ROCK inhibitors (Fasudil) and inducer of definitive endoderm 1 (IDE1) can promote differentiation of definitive endoderm, but their effects remain controversial. Therefore, we attempted to verify the effect of these small molecules on promoting definitive endoderm differentiation and found that Fasudil or IDE1 alone could not achieve a similar effect as activin A. On the contrary, CHIR99021 could efficiently promote definitive endoderm differentiation. Nearly 43.4% of experimental cells were SRY-box transcription factor 17 (SOX17)-positive under the synergistic effect of IDE1 and CHIR99021, but its ability to differentiate towards definitive endoderm was still insufficient...

PURPOSE: Cerebral ischemia-reperfusion (I/R) is a neurovascular disorder that leads to brain injury. In mice, Fasudil improves nerve injury induced by I/R. However, it is unclear if this is mediated by increased peroxisome proliferator-activated receptor-α (PPARα) expression and reduced oxidative damage. This study aimed to investigate the neuroprotective mechanism of action of Fasudil. METHODS: MCAO (Middle cerebral artery occlusion) was performed in male C57BL/6J wild-type and PPARα KO mice between September 2021 to April 2023...

The effects of Rho kinase inhibitors fasudil and ripasudil on arterial stiffness were assessed using anesthetized rabbits, where the aortic β and femoral β were measured as a stiffness parameter at each arterial region. Intravenous administration of fasudil and ripasudil dose-dependently decreased blood pressure and femoral vascular resistance and increased femoral arterial blood flow, which appeared according to their in vitro potencies for Rho kinase inhibition. Both drugs increased the aortic β but decreased the femoral β at hypotensive doses...

BACKGROUND AND PURPOSE: Various prophylactic drugs for cerebral vasospasm and delayed cerebral infarction (DCI) after subarachnoid hemorrhage (SAH) have been used in Japan. To investigate the treatment trends for cerebral vasospasm and frequency of DCI after SAH throughout Japan in 2021. METHODS: In 2021 we conducted an anonymous questionnaire survey on management for preventing cerebral vasospasm after aneurysmal SAH, and the frequency of DCI. The questionnaire was emailed to 955 certified neurosurgeons at 553 hospitals in Japan...

BACKGROUND: Alzheimer's disease (AD) is the most predominant form of dementia. Rho-associated coiled coil kinase (ROCK) inhibitor, fasudil, is one of the candidate drugs against the AD progression. OBJECTIVE: We aimed to investigate possible changes of AD associated markers in three-dimensional neuro-spheroids (3D neuro-spheroids) generated from induced pluripotent stem cells derived from AD patients or healthy control subjects (HC) and to determine the impact of pharmacological intervention with the ROCK inhibitor fasudil...

AIMS: Protein kinase D (PKD), once considered an effector of protein kinase C (PKC), now plays many pathophysiological roles in various tissues. However, little is known about role of PKD in vascular function. We investigated the role of PKD in contraction of rat aorta and human aortic smooth muscle cells (HASMCs) and in haemodynamics in rats. METHODS AND RESULTS: Isometric tension of rat aortic was measured to examine norepinephrine-induced contraction in the presence of PKD, PKC and Rho-kinase inhibitors...

Schizophrenia is one of the most serious psychiatric disorders and is characterized by reductions in both brain volume and spine density in the frontal cortex. RhoA belongs to the RAS homolog (Rho) family and plays critical roles in neuronal development and structural plasticity via Rho-kinase. RhoA activity is regulated by GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs). Several variants in GAPs and GEFs associated with RhoA have been reported to be significantly associated with schizophrenia...

This research aimed to the study influence of fasudil (FAS) on myocardial fibrosis in rats with diabetes mellitus (DM) via the transforming growth factor-beta 1 (TGF-β1)/ small mothers against decapentaplegic (Smad) signaling pathway. A total of 30 Sprague-Dawley rats were randomly divided into a blank control group (Control group, n=10), DM model group (DM group, n=10) and FAS treatment group (FAS group, n=10), and their blood and myocardial tissues were collected. Then blood glucose (GLU) content, hepatic and myocardial function indexes, ejection fraction (EF) and other cardiac function parameters were detected, and ELISA was employed to determine the content of serum IL-6, IL-1 and TNF-α...

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease without early diagnostic and specific therapeutic approaches. Podocyte apoptosis and loss play important roles in the pathological process of DKD. This study aimed to explore whether urinary exosomes from type 2 diabetes patients with DKD could induce podocyte apoptosis and the underlying pathological mechanisms. The exosomes were isolated from the urine samples of patients with DKD (DKD-Exo). Later, they were taken up and internalized by MPC5 cells...

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive, cureless disease, characterized by increased pulmonary vascular resistance and remodeling, with subsequent ventricular dilatation and failure. New therapeutic targets are being investigated for their potential roles in improving PAH patients' symptoms and reversing pulmonary vascular pathology. METHOD: We aimed to address the available knowledge from the published randomized controlled trials (RCTs) regarding the role of Rho-kinase (ROCK) inhibitors, bone morphogenetic protein 2 (BMP2) inhibitors, estrogen inhibitors, and AMP-activated protein kinase (AMPK) activators on the PAH evaluation parameters...

OBJECTIVE: To investigate the effect of butylphthalide combined with fasudil in the treatment of subarachnoid hemorrhage (SAH) with cerebral vasospasm (CVS) on inflammatory factors, cognitive function and vascular endothelial function. METHODS: It is a retrospective study in which a total of 104 patients with SAH with CVS admitted to Baoding First Central Hospital from July 2020 to February 2022 were selected and randomly divided into two groups by drawing lots...

Acetaminophen (APAP) overdoses can cause severe liver injury. In this study, the protective effect of fasudil against APAP-induced liver injury was investigated. APAP (400 mg/kg) was administered to male C57BL/6J mice to induce liver injury, and fasudil (20 or 40 mg/kg) was injected 30 min before APAP administration. Fasudil markedly suppressed APAP-induced elevation in serum transaminase activity and hepatic necrosis and significantly reduced an increase in nitrotyrosine and DNA fragmentation...

BACKGROUND: Despite the approval of several medications for pulmonary hypertension, morbidity and mortality are unacceptably high. Systemic hypotension may limit the use of pulmonary hypertension medications. OBJECTIVES: This study aimed to assess whether the homing peptide CAR (CARSKNKDC) improves the vasodilatory selectivity of fasudil in the pulmonary circulation or systemic circulation in a porcine pulmonary hypertension model. MATERIALS AND METHODS: Pulmonary hypertension (to approximately 2/3-3/4 systemic pressure levels) was induced by chronic and acute administration of microspheres in 3 micro Yucatan pigs (mean weight 19...

BACKGROUND: Antiphospholipid syndrome (APS) is a group of clinical syndromes of thrombosis or adverse pregnancy outcomes caused by antiphospholipid antibodies, which increase the incidence of in vitro fertilization failure in patients with infertility. However, the common mechanism of repeated implantation failure (RIF) with APS is unclear. This study aimed to search for potential diagnostic genes and potential therapeutic targets for RIF with APS. METHODS: To obtain differentially expressed genes (DEGs), we downloaded the APS and RIF datasets separately from the public Gene Expression Omnibus database and performed differential expression analysis...

OBJECTIVES: Fibroses are disorders linked to persistence of myofibroblasts due to biochemical (e.g., Transforming growth factor-β) and biophysical cues (e.g., a stiff microenvironment). In the context of osteoarthritis, fibrotic changes in the joint-lining synovium have been linked with disease progression. The objective of this study was to probe synovial fibroblast mechanobiology and how essential functions (i.e., lubrication) are altered in fibrotic environments. DESIGN: Both ex vivo and in vitro synovium models were assessed for fibrotic and lubrication biomarkers to better understand the role of mechanobiology and lubrication...

Emerging cell-based therapies such as CAR-T (Chimeric Antigen Receptor T) cells require cryopreservation to store and deliver intact and viable cells. Conventional cryopreservation formulations use DMSO to mitigate cold-induced damage, but do not address all the biochemical damage mechanisms induced by cold stress, such as programmed cell death (apoptosis). Rho-associated protein kinases (ROCK) are a key component of apoptosis, and their activation contributes to apoptotic blebbing. Here we demonstrate that the ROCK inhibitor fasudil hydrochloride, when supplemented into the thawing medium of T-cells increases the overall yield of healthy cells...