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Keywords = lipophilic statin

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13 pages, 6867 KiB  
Article
Association Between Statin Use and Psoriasis in Patients with Dyslipidemia: A Korean National Health Screening Cohort Study
by Kyeong Min Han, Mi Jung Kwon, Hyo Geun Choi, Ji Hee Kim, Joo-Hee Kim, Dae Myoung Yoo, Na-Eun Lee and Ho Suk Kang
J. Clin. Med. 2025, 14(1), 91; https://doi.org/10.3390/jcm14010091 - 27 Dec 2024
Viewed by 1219
Abstract
Background/Objectives: Psoriasis is a chronic inflammatory disease that significantly impacts physical and emotional health. Statins, primarily used as lipid-lowering drugs, have also demonstrated anti-inflammatory effects. While some studies suggest that statins may improve psoriasis symptoms, the findings have been inconsistent. This study aims [...] Read more.
Background/Objectives: Psoriasis is a chronic inflammatory disease that significantly impacts physical and emotional health. Statins, primarily used as lipid-lowering drugs, have also demonstrated anti-inflammatory effects. While some studies suggest that statins may improve psoriasis symptoms, the findings have been inconsistent. This study aims to investigate the association between prior statin use and the onset of psoriasis in a Korean population, focusing on individuals with dyslipidemia to minimize confounding factors. Methods: Using the Korean Health Insurance database (2002–2019), a nationwide nested case-control study was conducted, enrolling 8285 participants with psoriasis and 33,140 controls, matched 1:4 for sex, age, residence, and income through propensity scoring. Results: Adjusted odds ratios revealed significantly lower risks of psoriasis among short-term statin users (OR = 0.70, 95% CI = 0.66–0.74) and long-term users (OR = 0.77, 95% CI = 0.73–0.82) than in nonusers. This trend was consistent for both lipophilic and hydrophilic statins, and across subgroup analyses. Conclusions: These findings suggest that statins may reduce the incidence of psoriasis. However, further research is needed to assess their effects on psoriasis progression and severity. Full article
(This article belongs to the Section Epidemiology & Public Health)
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11 pages, 487 KiB  
Article
Statin Use in Metabolic Dysfunction-Associated Steatotic Liver Disease and Effects on Vibration-Controlled Transient Elastography-Derived Scores—A Population-Based Inverse Probability Treatment Weighting Analysis
by Natchaya Polpichai, Sakditad Saowapa, Aunchalee Jaroenlapnopparat, Leandro Sierra, Pojsakorn Danpanichkul, Panisara Fangsaard, Phuuwadith Wattanachayakul and Apichat Kaewdech
Livers 2024, 4(4), 677-687; https://doi.org/10.3390/livers4040046 - 12 Dec 2024
Viewed by 3167
Abstract
Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease globally. The impact of statins on liver fibrosis severity in MASLD individuals remains uncertain, despite their known cardiovascular benefits. Methods: A cross-sectional study was performed utilizing the National [...] Read more.
Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease globally. The impact of statins on liver fibrosis severity in MASLD individuals remains uncertain, despite their known cardiovascular benefits. Methods: A cross-sectional study was performed utilizing the National Health and Nutrition Examination Survey (NHANES) database from 2017 to 2018. MASLD was defined by hepatic steatosis (controlled attenuation parameter [CAP] score ≥ 288 dB/m) without other etiologies. Using inverse probability treatment weighting to minimize confounding, we examined the association between statin use and MASLD outcomes, including at-risk steatohepatitis (FibroScan-aspartate aminotransferase [AST] [FAST] score ≥ 0.67), significant and advanced fibrosis (liver stiffness measurement [LSM] ≥ 8.8 kilopascals [kPa] and ≥ 11.7 kPa), and advanced fibrosis (AGILE 3+ score ≥ 0.68). Results: Of 1283 MASLD patients, 376 were prescribed statins within the past 30 days. After adjustment for confounders, statin use was significantly associated with reduced risks of at-risk steatohepatitis, significant fibrosis, and high AGILE 3+ scores, with odds ratios (ORs) of 0.29 (95% CI: 0.01 to 0.87), 0.54 (95% CI: 0.31 to 0.95), and 0.41 (95% CI: 0.22 to 0.75), respectively. However, a subgroup analysis showed this effect persisted only with lipophilic statins. Conclusions: Statin use was associated with reduced steatohepatitis and fibrosis in patients with MASLD, supported by robust causal inference and vibration-controlled transient elastography-derived scores. Full article
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17 pages, 5189 KiB  
Article
The Association between Statin Use and Reduced Migraine Likelihood: A Comprehensive Analysis of Migraine Subtypes and Statin Types in a Nationwide Korean Cohort
by Ho Suk Kang, Joo-Hee Kim, Ji Hee Kim, Woo Jin Bang, Dae Myoung Yoo, Na-Eun Lee, Kyeong Min Han, Nan Young Kim, Hyo Geun Choi, Kyueng-Whan Min and Mi Jung Kwon
Pharmaceuticals 2024, 17(8), 1056; https://doi.org/10.3390/ph17081056 - 10 Aug 2024
Cited by 2 | Viewed by 2217
Abstract
Despite growing interest in the preventive effects of statins, as lipid-lowering agents, on migraine attacks, comprehensive nationwide studies comparing migraine likelihood between statin users and controls are lacking. Our nested case–control study within the Korean National Health Insurance Service-Health Screening Cohort (2002–2019) investigated [...] Read more.
Despite growing interest in the preventive effects of statins, as lipid-lowering agents, on migraine attacks, comprehensive nationwide studies comparing migraine likelihood between statin users and controls are lacking. Our nested case–control study within the Korean National Health Insurance Service-Health Screening Cohort (2002–2019) investigated this association using 38,957 migraine patients and 155,828 controls, considering migraine subtypes (with/without aura) and statin types (lipophilic vs. hydrophilic). Using propensity score matching and adjusting for confounders, statin use was linked to reduced migraine likelihood overall (odds ratio (OR) 0.93), particularly for migraines with aura (OR 0.75) and without aura (OR 0.94). Lipophilic statins were effective for both subtypes, while hydrophilic statins mainly reduced the likelihood of migraines without aura. Subgroup analyses showed consistent benefits across demographics, but varied effectiveness based on weight, smoking, alcohol use, hemoglobin levels, and dyslipidemia history. In summary, this nationwide cohort study suggests that statin use may reduce migraine likelihood among Korean adults across diverse demographics and clinical profiles, but varied effectiveness based on certain lifestyle and comorbidity factors underscores the importance of considering individual patient profiles when assessing the potential benefits of statin therapy for migraine prevention. Full article
(This article belongs to the Special Issue Pharmacological Modulation of Lipoproteins)
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14 pages, 3127 KiB  
Article
Effect of Statin Lipophilicity on the Proliferation of Hepatocellular Carcinoma Cells
by Goda Glebavičiūtė, Akshay Kumar Vijaya and Giulio Preta
Biology 2024, 13(6), 455; https://doi.org/10.3390/biology13060455 - 19 Jun 2024
Cited by 1 | Viewed by 2286
Abstract
The HMG-CoA reductase inhibitors, statins, are drugs used globally for lowering the level of cholesterol in the blood. Different clinical studies of statins in cancer patients have indicated a decrease in cancer mortality, particularly in patients using lipophilic statins compared to those on [...] Read more.
The HMG-CoA reductase inhibitors, statins, are drugs used globally for lowering the level of cholesterol in the blood. Different clinical studies of statins in cancer patients have indicated a decrease in cancer mortality, particularly in patients using lipophilic statins compared to those on hydrophilic statins. In this paper, we selected two structurally different statins (simvastatin and pravastatin) with different lipophilicities and investigated their effects on the proliferation and apoptosis of hepatocellular carcinoma cells. Lipophilic simvastatin highly influences cancer cell growth and survival in a time- and concentration-dependent manner, while pravastatin, due to its hydrophilic structure and limited cellular uptake, showed minimal cytotoxic effects. Full article
(This article belongs to the Section Medical Biology)
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21 pages, 1104 KiB  
Review
Statins—Their Role in Bone Tissue Metabolism and Local Applications with Different Carriers
by Marcin Mateusz Granat, Joanna Eifler-Zydel and Joanna Kolmas
Int. J. Mol. Sci. 2024, 25(4), 2378; https://doi.org/10.3390/ijms25042378 - 17 Feb 2024
Cited by 14 | Viewed by 3035
Abstract
Statins, widely prescribed for lipid disorders, primarily target 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase competitively and reversibly, resulting in reduced low-density lipoprotein cholesterol (LDL-C). This mechanism proves effective in lowering the risk of lipid-related diseases such as ischemic cerebrovascular and coronary artery diseases. Beyond their [...] Read more.
Statins, widely prescribed for lipid disorders, primarily target 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase competitively and reversibly, resulting in reduced low-density lipoprotein cholesterol (LDL-C). This mechanism proves effective in lowering the risk of lipid-related diseases such as ischemic cerebrovascular and coronary artery diseases. Beyond their established use, statins are under scrutiny for potential applications in treating bone diseases. The focus of research centers mainly on simvastatin, a lipophilic statin demonstrating efficacy in preventing osteoporosis and aiding in fracture and bone defect healing. Notably, these effects manifest at elevated doses (20 mg/kg/day) of statins, posing challenges for systematic administration due to their limited bone affinity. Current investigations explore intraosseous statin delivery facilitated by specialized carriers. This paper outlines various carrier types, characterizing their structures and underscoring various statins’ potential as local treatments for bone diseases. Full article
(This article belongs to the Special Issue Feature Papers in Molecular Endocrinology and Metabolism)
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17 pages, 5600 KiB  
Article
The Impact of Statins on the Survival of Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib or Lenvatinib
by Ji Eun Han, Jisu Kim, Jae Youn Cheong, Soon Sun Kim, Sun Gyo Lim, Min Jae Yang, Choong-Kyun Noh, Gil Ho Lee, Jung Woo Eun, Bumhee Park and Hyo Jung Cho
Cancers 2024, 16(2), 249; https://doi.org/10.3390/cancers16020249 - 5 Jan 2024
Cited by 2 | Viewed by 2211
Abstract
We aimed to evaluate the survival benefits of coadministering statins and multityrosine kinase inhibitors (TKIs) in patients with advanced hepatocellular carcinoma (HCC). Data from the Health Insurance Review and Assessment Service in Korea (2010–2020) were utilized. Statin use (≥28 cumulative defined daily doses) [...] Read more.
We aimed to evaluate the survival benefits of coadministering statins and multityrosine kinase inhibitors (TKIs) in patients with advanced hepatocellular carcinoma (HCC). Data from the Health Insurance Review and Assessment Service in Korea (2010–2020) were utilized. Statin use (≥28 cumulative defined daily doses) was analyzed, with 1534 statin users matched to 6136 non-users (1:4 ratio) using propensity scores. Primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS). Statin use significantly improved OS (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.72–0.82, p < 0.001) and PFS (HR 0.78, 95% CI 0.74–0.84, p < 0.001). Continuous or post-TKI statin users had better OS, while discontinuation after TKI use led to poorer OS. Both lipophilic and hydrophilic statins improved OS and PFS, particularly with ≥730 cumulative defined daily doses. In conclusion, combining statins and TKIs in patients with advanced HCC yielded significant survival benefits, influenced by statin dosage and duration. Continuous statin administration post-TKI treatment is crucial for improving outcomes in patients with HCC. Full article
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21 pages, 3197 KiB  
Article
Lipophilic Statins Eliminate Senescent Endothelial Cells by inducing Anoikis-Related Cell Death
by Barbora Belakova, Nicholas K. Wedige, Ezzat M. Awad, Simon Hess, André Oszwald, Marlene Fellner, Shafaat Y. Khan, Ulrike Resch, Markus Lipovac, Karel Šmejkal, Pavel Uhrin and Johannes M. Breuss
Cells 2023, 12(24), 2836; https://doi.org/10.3390/cells12242836 - 14 Dec 2023
Cited by 9 | Viewed by 3171
Abstract
Pre-clinical studies from the recent past have indicated that senescent cells can negatively affect health and contribute to premature aging. Targeted eradication of these cells has been shown to improve the health of aged experimental animals, leading to a clinical interest in finding [...] Read more.
Pre-clinical studies from the recent past have indicated that senescent cells can negatively affect health and contribute to premature aging. Targeted eradication of these cells has been shown to improve the health of aged experimental animals, leading to a clinical interest in finding compounds that selectively eliminate senescent cells while sparing non-senescent ones. In our study, we identified a senolytic capacity of statins, which are lipid-lowering drugs prescribed to patients at high risk of cardiovascular events. Using two different models of senescence in human vascular endothelial cells (HUVECs), we found that statins preferentially eliminated senescent cells, while leaving non-senescent cells unharmed. We observed that the senolytic effect of statins could be negated with the co-administration of mevalonic acid and that statins induced cell detachment leading to anoikis-like apoptosis, as evidenced by real-time visualization of caspase-3/7 activation. Our findings suggest that statins possess a senolytic property, possibly also contributing to their described beneficial cardiovascular effects. Further studies are needed to explore the potential of short-term, high-dose statin treatment as a candidate senolytic therapy. Full article
(This article belongs to the Special Issue Senescence in the Cardiovascular System)
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12 pages, 1034 KiB  
Article
Correlation between Statin Solubility and Mortality in Patients on Chronic Hemodialysis
by Seok-Hui Kang, Gui-Ok Kim, Bo-Yeon Kim, Eun-Jung Son and Jun-Young Do
Diagnostics 2023, 13(20), 3290; https://doi.org/10.3390/diagnostics13203290 - 23 Oct 2023
Cited by 2 | Viewed by 1637
Abstract
This study aimed to evaluate the effect of statin solubility on the survival of patients undergoing hemodialysis (HD). This retrospective study used laboratory and clinical data from a national HD quality assessment program and claims data (n = 53,345). The use of [...] Read more.
This study aimed to evaluate the effect of statin solubility on the survival of patients undergoing hemodialysis (HD). This retrospective study used laboratory and clinical data from a national HD quality assessment program and claims data (n = 53,345). The use of statins was defined as prescription ≥30 days during 6 months of each HD quality assessment period. We divided the patients into three groups based on the use and solubility of statins: No group, patients without a prescription of statins (n = 37,944); Hydro group, patients with a prescription of hydrophilic statins (n = 2823); and Lipo group, patients with a prescription of lipophilic statins (n = 12,578). The 5-year survival rates in the No, Hydro, and Lipo groups were 69.6%, 67.9%, and 67.9%, respectively (p < 0.001 for the trend). Multivariable Cox regression analyses showed that the Lipo group had better patient survival than the No group. However, multivariable analyses did not show statistical significance between the Hydro and No or Lipo groups. In all subgroups based on sex, age, presence of diabetes mellitus, and heart disease, the Lipo group had better patient survival than the No group. We identified no significant association between hydrophilic and lipophilic statins and patient survival. However, patients taking lipophilic statins had a modest survival benefit compared with those who did not receive statins. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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26 pages, 1766 KiB  
Review
The Potential Therapeutic Application of Simvastatin for Brain Complications and Mechanisms of Action
by Yen My Vuu, Ashraf Kadar Shahib and Mojgan Rastegar
Pharmaceuticals 2023, 16(7), 914; https://doi.org/10.3390/ph16070914 - 22 Jun 2023
Cited by 11 | Viewed by 7309
Abstract
Statins are common drugs that are clinically used to reduce elevated plasma cholesterol levels. Based on their solubility, statins are considered to be either hydrophilic or lipophilic. Amongst them, simvastatin has the highest lipophilicity to facilitate its ability to cross the blood-brain barrier. [...] Read more.
Statins are common drugs that are clinically used to reduce elevated plasma cholesterol levels. Based on their solubility, statins are considered to be either hydrophilic or lipophilic. Amongst them, simvastatin has the highest lipophilicity to facilitate its ability to cross the blood-brain barrier. Recent studies have suggested that simvastatin could be a promising therapeutic option for different brain complications and diseases ranging from brain tumors (i.e., medulloblastoma and glioblastoma) to neurological disorders (i.e., Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease). Specific mechanisms of disease amelioration, however, are still unclear. Independent studies suggest that simvastatin may reduce the risk of developing certain neurodegenerative disorders. Meanwhile, other studies point towards inducing cell death in brain tumor cell lines. In this review, we outline the potential therapeutic effects of simvastatin on brain complications and review the clinically relevant molecular mechanisms in different cases. Full article
(This article belongs to the Special Issue Statins Use and Cancer)
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11 pages, 473 KiB  
Article
Relation of Statin Use with Esophageal Cancer
by Sarang Jang, Hyo Geun Choi, Mi Jung Kwon, Ji Hee Kim, Joo-Hee Kim and So Young Kim
Pharmaceuticals 2023, 16(6), 900; https://doi.org/10.3390/ph16060900 - 19 Jun 2023
Viewed by 1998
Abstract
The present study evaluated the association of long-term statin use with the diagnosis and mortality of esophageal cancer in a Korean population. The Korean National Health Insurance Service-Health Screening Cohort from 2002 to 2019 was enrolled. Esophageal cancer patients were matched with control [...] Read more.
The present study evaluated the association of long-term statin use with the diagnosis and mortality of esophageal cancer in a Korean population. The Korean National Health Insurance Service-Health Screening Cohort from 2002 to 2019 was enrolled. Esophageal cancer patients were matched with control participants for demographic variables. The statin prescription histories were collected and grouped into <180 days, 180 to 545 days, and >545 days of duration. Propensity score overlap weighting was applied to minimize the bias between the esophageal cancer and control groups. The odds ratios (ORs) of the duration of statin use for esophageal cancer were analyzed using propensity score overlap weighted multivariable logistic regression analysis. The esophageal cancer group was classified as dead and surviving patients, and the ORs of the duration of statin use for the mortality of esophageal cancer were analyzed in an identical manner. Secondary analyses were conducted according to comorbid factors. Patients with esophageal cancer did not show lower odds for the duration of statin prescription in the overall study population (OR = 1.30, 95% CI = 1.03–1.65, p = 0.027 for 180 to 545 days and OR = 1.29, 95% CI = 1.08–1.55, p = 0.006 for >545 days). Subgroups of nonsmokers, past and current smokers, alcohol consumption ≥ 1 time a week, SBP < 140 mmHg and DBP < 90 mmHg, fasting blood glucose ≥ 100 mg/dL, total cholesterol ≥ 200 mg/dL, CCI score = 0, and nondyslipidemia history demonstrated low odds for the duration of statin prescription. Both types of statins, hydrophilic and lipophilic statins, were not related to a lower rate of esophageal cancer. The mortality of esophageal cancer was not associated with the duration of statin prescription. A subgroup with total cholesterol ≥ 200 mg/dL showed lower odds of statin prescription for mortality of esophageal cancer. The duration of statin prescription was not related to a lower rate or mortality of esophageal cancer in the adult Korean population. Full article
(This article belongs to the Special Issue Adjuvant Therapies for Cancer Treatment)
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15 pages, 1167 KiB  
Article
The Association between Statins and Liver Cancer Risk in Patients with Heart Failure: A Nationwide Population-Based Cohort Study
by Meng-Chuan Lu, Chun-Chao Chen, Meng-Ying Lu, Kuan-Jie Lin, Chun-Chih Chiu, Tsung-Yeh Yang, Yu-Ann Fang, William Jian, Ming-Yao Chen, Min-Huei Hsu, Yu-Hsin Lai, Tsung-Lin Yang, Wen-Rui Hao and Ju-Chi Liu
Cancers 2023, 15(11), 2959; https://doi.org/10.3390/cancers15112959 - 29 May 2023
Cited by 3 | Viewed by 2354
Abstract
Heart failure (HF) and cancer have similar risk factors. HMG-CoA reductase inhibitors, also known as statins, are chemoprotective agents against carcinogenesis. We aimed to evaluate the chemoprotective effects of statins against liver cancer in patients with HF. This cohort study enrolled patients with [...] Read more.
Heart failure (HF) and cancer have similar risk factors. HMG-CoA reductase inhibitors, also known as statins, are chemoprotective agents against carcinogenesis. We aimed to evaluate the chemoprotective effects of statins against liver cancer in patients with HF. This cohort study enrolled patients with HF aged ≥20 years between 1 January 2001 and 31 December 2012 from the National Health Insurance Research Database in Taiwan. Each patient was followed to assess liver cancer risk. A total of 25,853 patients with HF were followed for a 12-year period; 7364 patients used statins and 18,489 did not. The liver cancer risk decreased in statin users versus non-users (adjusted hazard ratio (aHR) = 0.26, 95% confidence interval (CI): 0.20–0.33) in the entire cohort in the multivariate regression analysis. In addition, both lipophilic and hydrophilic statins reduced the liver cancer risk in patients with HF (aHR 0.34, 95% CI: 0.26–0.44 and aHR 0.42, 95% CI: 0.28–0.54, respectively). In the sensitivity analysis, statin users in all dose-stratified subgroups had a reduced liver cancer risk regardless of age, sex, comorbidity, or other concomitant drug use. In conclusion, statins may decrease liver cancer risk in patients with HF. Full article
(This article belongs to the Section Cancer Epidemiology and Prevention)
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12 pages, 1176 KiB  
Article
Association between Gallstone Disease and Statin Use: A Nested Case—Control Study in Korea
by Mi Jung Kwon, Jung Woo Lee, Ho Suk Kang, Hyun Lim, Eun Soo Kim, Nan Young Kim, Hyo Geun Choi and Min-Jeong Kim
Pharmaceuticals 2023, 16(4), 536; https://doi.org/10.3390/ph16040536 - 3 Apr 2023
Cited by 3 | Viewed by 5072
Abstract
The correlation between statin use and the development of gallstone disease remains controversial. Existing data, primarily based on Caucasian populations, are biased, thus necessitating validation studies involving Asian cohorts. We conducted a nested case–control study using data from the Korean National Health Insurance [...] Read more.
The correlation between statin use and the development of gallstone disease remains controversial. Existing data, primarily based on Caucasian populations, are biased, thus necessitating validation studies involving Asian cohorts. We conducted a nested case–control study using data from the Korean National Health Insurance Service Health Screening Cohort (2002–2019) to determine the likelihood of gallstone disease according to periods of previous statin use and type of statin. Among the 514,866 participants, 22,636 diagnosed with gallstones at ≥2 clinic visits (using the International Classification of Diseases, 10th revision, code K80) were matched 1:4 to 90,544 controls for age, sex, income, and residential area, and their statin prescription history for 2 years prior to the index date was examined. Propensity-score-weighted odds ratios (ORs) for gallstone disease were calculated using conditional logistic regression. Long-term use (>545 days) of any statin or lipophilic statins was associated with lower odds of incident gallstones (OR = 0.91, 95% confidence interval [CI] = 0.86–0.96, p < 0.001 and OR = 0.88, 95% CI = 0.83–0.93, p < 0.001, respectively) after adjusting for confounders. Short-term use (180–545 days) of any statin or hydrophilic statins was not statistically related to incident gallstones. In summary, prior statin medication, particularly long-term lipophilic statin use, may confer a preventive advantage against gallstone disease. Full article
(This article belongs to the Special Issue Enzyme Inhibitors: Potential Therapeutic Approaches)
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19 pages, 4713 KiB  
Article
Effects of Mineralocorticoid Receptor Blockade and Statins on Kidney Injury Marker 1 (KIM-1) in Female Rats Receiving L-NAME and Angiotensin II
by Jiayan Huang, Ezgi Caliskan Guzelce, Shadi K. Gholami, Kara L. Gawelek, Richard N. Mitchell, Luminita H. Pojoga, Jose R. Romero, Gordon H. Williams and Gail K. Adler
Int. J. Mol. Sci. 2023, 24(7), 6500; https://doi.org/10.3390/ijms24076500 - 30 Mar 2023
Cited by 3 | Viewed by 3095
Abstract
Kidney injury molecule-1 (KIM-1) is a biomarker of renal injury and a predictor of cardiovascular disease. Aldosterone, via activation of the mineralocorticoid receptor, is linked to cardiac and renal injury. However, the impact of mineralocorticoid receptor activation and blockade on KIM-1 is uncertain. [...] Read more.
Kidney injury molecule-1 (KIM-1) is a biomarker of renal injury and a predictor of cardiovascular disease. Aldosterone, via activation of the mineralocorticoid receptor, is linked to cardiac and renal injury. However, the impact of mineralocorticoid receptor activation and blockade on KIM-1 is uncertain. We investigated whether renal KIM-1 is increased in a cardiorenal injury model induced by L-NAME/ANG II, and whether mineralocorticoid receptor blockade prevents the increase in KIM-1. Since statin use is associated with lower aldosterone, we also investigated whether administering eiSther a lipophilic statin (simvastatin) or a hydrophilic statin (pravastatin) prevents the increase in renal KIM-1. Female Wistar rats (8–10 week old), consuming a high salt diet (1.6% Na+), were randomized to the following conditions for 14 days: control; L-NAME (0.2 mg/mL in drinking water)/ANG II (225 ug/kg/day on days 12–14); L-NAME/ANG II + eplerenone (100 mg/kg/day p.o.); L-NAME/ANG II + pravastatin (20 mg/kg/day p.o.); L-NAME/ANG II + simvastatin (20 mg/kg/day p.o.). Groups treated with L-NAME/ANG II had significantly higher blood pressure, plasma and urine aldosterone, cardiac injury/stroke composite score, and renal KIM-1 than the control group. Both eplerenone and simvastatin reduced 24-h urinary KIM-1 (p = 0.0046, p = 0.031, respectively) and renal KIM-1 immunostaining (p = 0.004, p = 0.037, respectively). Eplerenone also reduced renal KIM-1 mRNA expression (p = 0.012) and cardiac injury/stroke composite score (p = 0.04). Pravastatin did not affect these damage markers. The 24-h urinary KIM-1, renal KIM-1 immunostaining, and renal KIM-1 mRNA expression correlated with cardiac injury/stroke composite score (p < 0.0001, Spearman ranked correlation = 0.69, 0.66, 0.59, respectively). In conclusion, L-NAME/ANG II increases renal KIM-1 and both eplerenone and simvastatin blunt this increase in renal KIM-1. Full article
(This article belongs to the Special Issue Cardiovascular Endocrinology Research)
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13 pages, 1903 KiB  
Article
Effects of Statin Combinations on Zika Virus Infection in Vero Cells
by Erica Españo and Jeong-Ki Kim
Pharmaceutics 2023, 15(1), 50; https://doi.org/10.3390/pharmaceutics15010050 - 23 Dec 2022
Cited by 6 | Viewed by 2278
Abstract
The Zika virus (ZIKV) remains a global health concern. Thus far, no antiviral or vaccine has been approved to prevent or treat ZIKV infection. In a previous study, we found that lipophilic statins can inhibit ZIKV production in Vero cells. These statins appear [...] Read more.
The Zika virus (ZIKV) remains a global health concern. Thus far, no antiviral or vaccine has been approved to prevent or treat ZIKV infection. In a previous study, we found that lipophilic statins can inhibit ZIKV production in Vero cells. These statins appear to have different potencies against ZIKV infection. Here, we determined whether combinations of statins would have synergistic effects to maximize the efficacy of the statins and to reduce potential side effects. Specifically, we used a modified fixed-ratio assay for the combinations of atorvastatin (ATO) or fluvastatin (FLU) with mevastatin (MEV) or simvastatin (SIM). All combinations with MEV tended towards synergy, especially with higher fractions of MEV in the combinations. The ATO + SIM combination tended towards additivity. The FLU + SIM combination also tended towards additivity except for one combination which had the highest fraction of FLU over SIM among the tested combinations. Overall, certain combinations of ATO or FLU with SIM or MEV may be synergistic. More exhaustive combinatorial assays in vitro and in vivo could help define whether combining lipophilic statins would be beneficial and safe for treating ZIKV infections. Full article
(This article belongs to the Special Issue Drugs for Antiviral Combination Therapy)
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11 pages, 1346 KiB  
Article
Comparison of the Treatment Efficacy of Rosuvastatin versus Atorvastatin Loading Prior to Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction
by Esraa M. Adel, Ahmed A. Elberry, Ahmed Abdel Aziz, Ibrahim A. Naguib, Badrah S. Alghamdi and Raghda R. S. Hussein
J. Clin. Med. 2022, 11(17), 5142; https://doi.org/10.3390/jcm11175142 - 31 Aug 2022
Cited by 4 | Viewed by 2299
Abstract
The aim of this study was to compare the effect of a single high-dose rosuvastatin versus atorvastatin preloading in ST-elevation myocardial infarction (STEMI) patients receiving primary percutaneous coronary intervention (PCI.) Methods: A total of 99 patients presented with STEMI and were randomly divided [...] Read more.
The aim of this study was to compare the effect of a single high-dose rosuvastatin versus atorvastatin preloading in ST-elevation myocardial infarction (STEMI) patients receiving primary percutaneous coronary intervention (PCI.) Methods: A total of 99 patients presented with STEMI and were randomly divided into three groups—a control group (n = 33) with no statin treatment, an atorvastatin group (n = 33) with a single 80 mg atorvastatin dose and the rosuvastatin group (n = 33) with a single 40 mg rosuvastatin dose in the emergency room (ER) prior to PCI. Post-interventional thrombolysis in myocardial infarction (TIMI) flow grade and corrected TIMI frame count (CTFC) were recorded, and ST-segment resolution was measured. Results: CTFC was significantly lower for the atorvastatin group (p-value < 0.01) than in the control group. A final TIMI flow grade 3 was achieved in 32 (97.0%) patients in the rosuvastatin group and 28 (84.8%) patients in the atorvastatin group compared with only 25 (75.8%) patients in the control group (p = 0.014). Peak CK-MB in the rosuvastatin group (263.2 [207.2–315.6]) and the atorvastatin group (208 [151.0–314.1]) was lower compared to that in the control group (398.4 [303.9–459.3]); p < 0.001. Conclusions: A single extensive dose of lipophilic atorvastatin prior to primary PCI in STEMI patients showed better improvement in microvascular myocardial perfusion compared to hydrophilic rosuvastatin. Full article
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