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International Angiology 2021 June;40(3):248-60

DOI: 10.23736/S0392-9590.21.04632-0


language: English

PCSK9 inhibition, LDL and lipopolysaccharides: a complex and “dangerous” relationship

Raimondo FEMINÒ 1, Giovanni FEMINÒ 2, Attilio CAVEZZI 3 , Emidio TROIANI 4

1 Anesthesia and Intensive Care Unit, Department of General and Specialist Surgeries, Polyclinic of Modena, Modena, Italy; 2 Division of Immunology, Euro Medical Center Srl, Florence, Italy; 3 Eurocenter Venalinfa, San Benedetto del Tronto, Ascoli Piceno, Italy; 4 Unit of Cardiology, Social Security Institute, State Hospital, Cailungo, San Marino

Literature concerning the causative factors of atherosclerotic cardiovascular disease shows complex and sometimes contrasting evidence. Most guidelines suggest a strategy aimed at lowering circulating low density lipoproteins (LDL) and ApoB lipoprotein levels. The use of statins and of cholesteryl ester transfer protein inhibitors has led to a number of controversial outcomes, generating a certain degree of concern about the real efficacy and especially safety of these drugs. Literature data show that the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors results in a dramatic reduction of various markers of lipid metabolism (namely LDL); however, several critical scientific papers have questioned the value, the need and especially the safety of these innovative drugs. LDL are a protective factor against lipopolysaccharides and other microbial derivatives. Similarly, these gram-negative bacteria-derived compounds have been identified as probable culprits of cardiovascular atherogenesis; moreover, lipopolysaccharides increase hepatic synthesis of PCSK9, as defense mechanism. This enzyme modulates LDL receptors level in the liver, as well as in other organs, such as adrenal gland and reproductive organs. Hence, PCSK9 inhibition may influence glucocorticoid secretion and fertility. Lastly, the consequent reduction of circulating LDL may relevantly hindrance immune system and favor lipopolysaccharides diffusion.

KEY WORDS: PCSK9 protein, human; Lipopolysaccharides; Lipoproteins, LDL; Cardiovascular diseases

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