Recent Update on PCSK9 and Platelet Activation Experimental Research Methods: In Vitro and In Vivo Studies

Puteri, Meidi Utami; Azmi, Nuriza Ulul; Ridwan, Salbiah; Iqbal, Muhammad; Fatimah, Tresni; Rini, Tri Diana Puspita; Kato, Mitsuyasu; Saputri, Fadlina Chany

doi:10.3390/jcdd9080258

Cited by 2 publications

(1 citation statement)

References 48 publications

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“…The different components of a high-fat diet and duration of induction may influence the results. Nonetheless, our findings may pave the way for further research aimed at elucidating the correlation between nutrition intake, dyslipidemia, PCSK9, and platelet activation in the pathophysiology of atherosclerosis leading to myocardial infarction [61]. Our results are consistent with the findings of clinical studies, indicating that a high-fat diet resulting in hypercholesterolemia and hypertriglyceridemia is associated with a higher risk of platelet activation and elevated PCSK9 levels.…”

Section: Discussionsupporting

confidence: 88%

High-Fat Diet Enhances Platelet Activation and Is Associated with Proprotein Convertase Subtilisin Kexin 9: An Animal Study

Saputri,

Azmi,

Puteri

et al. 2023

Nutrients

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Platelet activation and proprotein convertase subtilisin kexin 9 (PCSK9) play pivotal roles in the progression of atherosclerosis to cardiovascular events. It has been reported that hyperlipidemia, a well-documented risk factors for cardiovascular diseases, tends increase platelet activation and PCSK9 expression. However, little is known about this specific mechanism, particularly how nutrition affects platelet activation and PCSK9 levels in hyperlipidemia conditions. This study aimed to assess how a high-fat diet influences platelet activation, its association with PCSK9, and the effects on blood pressure in an animal model. Here, male Wistar rats were divided into four groups, subjected to different high-fat diets for ten weeks with varying nutrient components. The results showed that high-fat diet-induced hypercholesterolemia and hypertriglyceridemia significantly increased the plasma levels of β-thromboglobulin (β-TG), p-selectin, and platelet factor 4 (PF-4). The blood pressure readings were also elevated post high-fat diet induction. Interestingly, the group with the highest percentage of saturated fatty acid and trans-fat exhibited the highest PCSK9 levels, along with the highest increase in plasma cholesterol, triglycerides, and platelet activation parameters. These findings confirm that high-fat diet-induced hypercholesterolemia and hypertriglyceridemia stimulate platelet activity and PCSK9 levels. Moreover, our results suggest that PCSK9, implicated in hypercholesterolemia and hypertriglyceridemia, may synergistically mediate platelet hyperactivity, aligning with clinical studies. Notably, our results highlight the association between a high-fat diet and PCSK9, providing insights for drug discovery targeting platelet activation in atherosclerosis-induced cardiovascular diseases.

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Section: Discussionsupporting

confidence: 88%

High-Fat Diet Enhances Platelet Activation and Is Associated with Proprotein Convertase Subtilisin Kexin 9: An Animal Study

Saputri,

Azmi,

Puteri

et al. 2023

Nutrients

Self Cite

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Proprotein convertase subtilisin/kexin type 9 (PCSK9) and clinical outcomes in dialysis patients

Torino,

Carbone,

Pizzini

et al. 2024

Eur J Clin Investigation

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BackgroundProprotein convertase subtilisin/kexin type 9 (PCSK9), a factor accelerating the degradation of LDL receptors, was associated with a gender‐dependent risk for cardiovascular (CV) events in the general population and with all‐cause and CV mortality in two relatively small studies in black Africans and South Korean haemodialysis patients. The effect modification by gender was untested in these studies.MethodsThe study enrolled 1188 dialysis patients from the Prospective Registry of The Working Group of Epidemiology of Dialysis Region Calabria (PROGREDIRE) cohort. PCSK9 was measured by colorimetric enzyme‐linked immunosorbent assay. The primary outcomes were all‐cause and CV mortality. Statistical analysis included Cox regression analysis and effect modification analysis.ResultsDuring a median 2.9‐year follow‐up, out of 494 deaths, 278 were CV‐related. In unadjusted analyses, PCSK9 levels correlated with increased all‐cause (HRfor1ln unit increase: 1.23, 95% CI 1.06–1.43, p =.008) and CV mortality (HRfor1ln unit increase: 1.26, 95% CI 1.03–1.54, p =.03). After multivariate adjustment, these associations were no longer significant (all‐cause mortality, HRfor 1 ln unit increase: 1.16, 95% CI .99–1.36, p =.07; CV mortality, HRfor1ln unit increase: 1.18, 95% CI .95–1.46, p =.14). However, in fully adjusted interaction analyses, a doubling in the risk of this outcome in women was registered (Women, HRfor1ln unit increase: 1.88, 95% CI 1.27–2.78, p =.002; Men, HRfor1ln unit increase: 1.07, 95% CI .83–1.38, p =.61; p for effect modification: .02).ConclusionsPCSK9 levels are unrelated to all‐cause mortality in haemodialysis patients but, like in studies of the general population, independently of other risk factors, entail a doubling in the risk of CV events in women in this population.

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Recent Update on PCSK9 and Platelet Activation Experimental Research Methods: In Vitro and In Vivo Studies

Cited by 2 publications

References 48 publications

High-Fat Diet Enhances Platelet Activation and Is Associated with Proprotein Convertase Subtilisin Kexin 9: An Animal Study

High-Fat Diet Enhances Platelet Activation and Is Associated with Proprotein Convertase Subtilisin Kexin 9: An Animal Study

Proprotein convertase subtilisin/kexin type 9 (PCSK9) and clinical outcomes in dialysis patients

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