PCSK9 and atherosclerosis burden in the coronary arteries of patients undergoing coronary angiography

Panahi, Yunes; Ghahrodi, Mohsen Sadeghi; Jamshir, Mohsen; Safarpour, Mohammad Amin; Bianconi, Vanessa; Pirro, Matteo; Farahani, Maryam Moshkani; Sahebkar, Amirhossein

doi:10.1016/j.clinbiochem.2019.09.001

Cited by 9 publications

(9 citation statements)

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“…The best-known function of PCSK9 is its effect on low density lipoprotein receptor (LDLR), to which it can bind and thereby facilitate its lysosomal degradation. Lately, PCSK9 is the focus of various studies in different clinical contexts as a marker for cardiovascular risks [13][14][15][16][17] independent of other known traditional risk factors and independent of its influence on LDLR. PCSK9 is thought to play an important role in cardiovascular diseases (CVDs) via different mechanisms, either through binding to Epidermal Growth Factor (EGF) domains on receptors or through binding with receptors present in lipid rafts and associated cell membrane micro-domains or by influencing the gene expression and protein response of various factors involved in the development of cardiac complications [18].…”

Section: Introductionmentioning

confidence: 99%

PCSK9: A Multi-Faceted Protein That Is Involved in Cardiovascular Biology

2021

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Pro-protein convertase subtilisin/kexin type 9 (PCSK9) is secreted mostly by hepatocytes and to a lesser extent by the intestine, pancreas, kidney, adipose tissue, and vascular cells. PCSK9 has been known to interact with the low-density lipoprotein receptor (LDLR) and chaperones the receptor to its degradation. In this manner, targeting PCSK9 is a novel attractive approach to reduce hyperlipidaemia and the risk for cardiovascular diseases. Recently, it has been recognised that the effects of PCSK9 in relation to cardiovascular complications are not only LDLR related, but that various LDLR-independent pathways and processes are also influenced. In this review, the various LDLR dependent and especially independent effects of PCSK9 on the cardiovascular system are discussed, followed by an overview of related PCSK9-polymorphisms and currently available and future therapeutic approaches to manipulate PCSK9 expression.

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Section: Introductionmentioning

confidence: 99%

PCSK9: A Multi-Faceted Protein That Is Involved in Cardiovascular Biology

2021

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“…Using the SYNTAX score to assess coronary severity is reasonable and meets the current guidelines, such as for use in myocardial infarction [ 19 , 32 ]. Recent studies have also shown that high levels of Pcsk9 can be considered as new and reliable biomarkers for the presence and severity of CHD [ 13 , 23 , 24 ]. Also, the circulating concentration of Pcsk9 increased in the first few hours/days after acute coronary syndrome (ACS) [ 23 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have also shown that high levels of Pcsk9 can be considered as new and reliable biomarkers for the presence and severity of CHD [ 13 , 23 , 24 ]. Also, the circulating concentration of Pcsk9 increased in the first few hours/days after acute coronary syndrome (ACS) [ 23 , 33 ]. Serum Pcsk9 levels are related to SYNTAX scores in patients with acute or stable CAD [ 20 – 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…Also, the circulating concentration of Pcsk9 increased in the first few hours/days after acute coronary syndrome (ACS) [ 23 , 33 ]. Serum Pcsk9 levels are related to SYNTAX scores in patients with acute or stable CAD [ 20 – 23 ]. The correlation between serum Pcsk9 levels and the extent of disease in PMI patients has not been studied until now.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, Pcsk9 may be directly related to atherosclerosis development [ 20 , 45 ]. Regarding possible direct atherosclerotic effects of Pcsk9, distinguishing the roles of Pcsk9 from those of LDL-C will be difficult, because it interferes with cholesterol metabolism very rapidly by enhancing LDLR degradation at different tissue levels [ 23 ]. Interestingly, the present study showed that, after stratifying by serum LDL-C level, medium-high Pcsk9 levels were only correlated with greater risk of high SYNTAX scores in patients with high LDL-C level, in whom this observation was not found.…”

Section: Discussionmentioning

confidence: 99%

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Pcsk9 is associated with severity of coronary artery lesions in male patients with premature myocardial infarction

et al. 2021

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Background Proprotein convertase subtilisin/kexin type 9 (Pcsk9) correlated with incidence and prognosis of coronary heart disease. However, it is unclear whether Pcsk9 contributed to coronary artery lesion severity in patients with premature myocardial infarction (PMI). The present study investigated associations between Pcsk9 and coronary artery lesion severity in PMI patients who underwent coronary angiography (CAG). Methods This prospective cohort study included young men (age ≤ 45 years, n = 332) with acute MI who underwent CAG between January 2017 and July 2019. Serum Pcsk9 levels and clinical characteristics were evaluated. SYNTAX scores (SYNergy between percutaneous coronary intervention with [paclitaxel-eluting] TAXUS stent and cardiac surgery) were calculated to quantify coronary artery lesions. Results Serum Pcsk9 levels were positively associated with SYNTAX scores (r = 0.173, P < 0.05). The diagnostic cutoff value of PSCK9 level was 122.9 ng/mL, yielding an area under the curve (AUC) of 0.63, sensitivity 81%, and specificity 40%. Serum Pcsk9, LDL-C, Apob, NT-proBnp, CK level, and diabetes history were independent predictors of high SYNTAX scores (P < 0.05). After stratifying by serum LDL-C level (cutoff = 2.6 mmol/L), medium-high Pcsk9 levels had increased risk of high SYNTAX scores in patients with high LDL-C (P < 0.05), and higher serum Pcsk9 levels had increased risk of major adverse cardiac events (MACE) after adjusting for confounding factors (P < 0.05). Conclusion Serum Pcsk9 levels correlates with severity of coronary artery lesion in PMI patients and may serve as a biomarker for severity of coronary artery stenosis in this patient population, which may contribute to risk stratification.

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