Interplay Between Statins, Cav1 (Caveolin-1), and Aldosterone

Haas, A. R. C.; Baudrand, René; Easly, Rebecca; Murray, Gillian; Touyz, Rhian M.; Pojoga, Luminita H.; Jeunemaı̂tre, Xavier; Hopkins, Paul N.; Rosner, Bernard; Williams, Jonathan S.; Williams, Gordon H.; Adler, Gail K.

doi:10.1161/hypertensionaha.120.14777

Cited by 6 publications

(5 citation statements)

References 31 publications

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“…It is also crucial for cholesterol transmembrane transport, accumulation and efflux; as it is the primary component of caveolae. In contrast with the current results, previous studies found that statin decreased the expression of CAV1 emphasizing a probable correlation between statins and CAV1 also suggesting a potential pleiotropic value of statins beside lipid reduction [ 64 ]. In contrast another study reported that statin increased CAV1 expression, but decreased the density of caveolae while the overall raft density was unaffected.…”

Section: Discussioncontrasting

confidence: 99%

The prognosis of lipid reprogramming with the HMG-CoA reductase inhibitor, rosuvastatin, in castrated Egyptian prostate cancer patients: Randomized trial

et al. 2022

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Aim The role of surgical castration and rosuvastatin treatment on lipid profile and lipid metabolism related markers was evaluated for their prognostic significance in metastatic prostate cancer (mPC) patients. Methods A total of 84 newly diagnosed castrated mPC patients treated with castration were recruited and divided into two groups: Group I served as control (statin non-users) while group II treated with Rosuvastatin (20 mg/day) for 6 months and served as statin users. Prostate specific antigen (PSA), epidermal growth factor receptor (EGFR), Caveolin-1 (CAV1), lipid profile (LDL, HDL, triglycerides (TG) and total cholesterol (TC)) and lipid metabolism related markers (aldoketoreductase (AKR1C4), HMG-CoA reductase (HMGCR), ATP-binding cassette transporter A1 (ABCA1), and soluble low density lipoprotein receptor related protein 1 (SLDLRP1)) were measured at baseline, after 3 and 6 months. Overall survival (OS) was analyzed by Kaplan-Meier and COX regression for prognostic significance. Results Before castration, HMG-CoA reductase was elevated in patients <65 years (P = 0.009). Bone metastasis was associated with high PSA level (P = 0.013), but low HMGCR (P = 0.004). Patients with positive family history for prostate cancer showed high levels of EGFR, TG, TC, LDL, alkaline phosphatase (ALP), but low AKR1C4, SLDLRP1, CAV1 and ABCA-1 levels. Smokers had high CAV1 level (P = 0.017). After 6 months of castration and rosuvastatin administration, PSA, TG, LDL and TC were significantly reduced, while AKR1C4, HMGCR, SLDLRP1, CAV1 and ABCA-1 were significantly increased. Overall survival was reduced in patients with high baseline of SLDLRP1 (>3385 pg/ml, P = 0.001), PSA (>40 ng/ml, P = 0.003) and CAV1 (>4955 pg/ml, P = 0.021). Conclusion Results of the current study suggest that the peripheral lipidogenic effects of rosuvastatin may have an impact on the treatment outcome and survival of castrated mPC patients. Trail registration This trial was registered at the Pan African Clinical Trial Registry with identification number PACTR202102664354163 and at ClinicalTrials.gov with identification number NCT04776889.

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Section: Discussioncontrasting

confidence: 99%

The prognosis of lipid reprogramming with the HMG-CoA reductase inhibitor, rosuvastatin, in castrated Egyptian prostate cancer patients: Randomized trial

et al. 2022

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“…It is possible that small decreases in aldosterone sufficient to modify KIM-1 levels did occur, but we were unable to detect these differences. In addition, it is possible that the stimulatory effects of a chronic ANG II infusion—a continuous ANG II infusion for three days longer than the duration of ANG II infusion in the previous human and animal studies [ 43 , 57 ]—may have partially overcome the inhibitory effects of simvastatin on aldosterone in the current study.…”

Section: Discussionmentioning

confidence: 93%

“…Second, since our previous study reported a decrease in aldosterone production by zona glomerulosa cells with simvastatin in male rats [ 43 ], there could be a biological sex difference in the relationship between simvastatin and aldosterone levels. However, two publications from our group showed no interaction between statin use and aldosterone levels with sex in humans [ 43 , 57 ]. Third, simvastatin could have an effect not only on reducing aldosterone production but also on MR activity.…”

Section: Discussionmentioning

confidence: 96%

Effects of Mineralocorticoid Receptor Blockade and Statins on Kidney Injury Marker 1 (KIM-1) in Female Rats Receiving L-NAME and Angiotensin II

Huang

Guzelce

Gholami

et al. 2023

IJMS

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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.

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“…The lipophilic statins atorvastatin and simvastatin appear to reduce angiotensin II sensitivity and to downregulate AT1R in humans [30]. Lipophilic statins (particularly simvastatin)-but not hydrophilic statins-are associated with lower aldosterone levels [29,31]. We speculate that the aldosterone-lowering effect may be another mechanism by which statins protect against aortic dissection.…”

Section: Study Strengths and Limitationsmentioning

confidence: 87%

Relationships between statins and risk reduction of aortic dissection in patients with hypertension

Dang,

Li,

Zhu

et al. 2023

Preprint

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Purpose Statins have cardiovascular protective effects in addition to lipid-lowering effects. However, no human studies have examined whether statins prevent aortic dissection. This study aimed to explore the association between statins and aortic dissection. Methods This nested case–control study was based on data extracted from the UHDATA (Hypertension Database at Urumchi) in Xinjiang of China. Cases (patients who developed aortic dissection) and controls (patients without aortic dissection; matched for age, sex, and date of aortic dissection diagnosis) were selected from among the 52,146 adult patients with hypertension and hyperlipidemia or high-risk hypertension registered in the database between January 1, 2006, and December 31, 2018. Follow-up data were collected up to April 30, 2022. Multivariable logistic regression analysis was used to assess the relationship between statin use and aortic dissection. Results A total of 7049 patients (75.6% men; mean age, 54.6 years) were selected for the study: 647 patients who developed aortic dissection during the follow-up period and 6402 patients who did not develop aortic dissection. The proportion of patients using statins was higher in the case group than in the control group (21.2% vs. 29.9%, P < 0.001). However, in multivariable logistic regression analysis, statin use was independently associated with decreased risk for aortic dissection (adjusted OR = 0.538, 95% CI: 0.418–0.692, P < 0.001). Conclusions Statins appear to reduce risk of aortic dissection, and clinicians should consider early use of statins in hypertensive patients, especially those with hyperlipidemia and multiple risk factors.

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Interplay Between Statins, Cav1 (Caveolin-1), and Aldosterone

Cited by 6 publications

References 31 publications

The prognosis of lipid reprogramming with the HMG-CoA reductase inhibitor, rosuvastatin, in castrated Egyptian prostate cancer patients: Randomized trial

The prognosis of lipid reprogramming with the HMG-CoA reductase inhibitor, rosuvastatin, in castrated Egyptian prostate cancer patients: Randomized trial

Effects of Mineralocorticoid Receptor Blockade and Statins on Kidney Injury Marker 1 (KIM-1) in Female Rats Receiving L-NAME and Angiotensin II

Relationships between statins and risk reduction of aortic dissection in patients with hypertension

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