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2. Plasma PCSK9 concentrations during an oral fat load and after short term high-fat, high-fat high-protein and high-fructose diets

Author

Cariou Bertrand, Langhi Cédric, Le Bras Maëlle, Bortolotti Murielle, Lê Kim-Anne, Theytaz Fanny, Le May Cédric, Guyomarc’h-Delasalle Béatrice, Zaïr Yassine, Kreis Roland, Boesch Chris, Krempf Michel, Tappy Luc, and Costet Philippe

Subjects
Nutrition, Dietary intervention, PCSK9, Insulin resistance, Liver steatosis, Nutrition. Foods and food supply, TX341-641, Nutritional diseases. Deficiency diseases, RC620-627
Abstract

Abstract Background PCSK9 (Proprotein Convertase Subtilisin Kexin type 9) is a circulating protein that promotes hypercholesterolemia by decreasing hepatic LDL receptor protein. Under non interventional conditions, its expression is driven by sterol response element binding protein 2 (SREBP2) and follows a diurnal rhythm synchronous with cholesterol synthesis. Plasma PCSK9 is associated to LDL-C and to a lesser extent plasma triglycerides and insulin resistance. We aimed to verify the effect on plasma PCSK9 concentrations of dietary interventions that affect these parameters. Methods We performed nutritional interventions in young healthy male volunteers and offspring of type 2 diabetic (OffT2D) patients that are more prone to develop insulin resistance, including: i) acute post-prandial hyperlipidemic challenge (n=10), ii) 4 days of high-fat (HF) or high-fat/high-protein (HFHP) (n=10), iii) 7 (HFruc1, n=16) or 6 (HFruc2, n=9) days of hypercaloric high-fructose diets. An acute oral fat load was also performed in two patients bearing the R104C-V114A loss-of-function (LOF) PCSK9 mutation. Plasma PCSK9 concentrations were measured by ELISA. For the HFruc1 study, intrahepatocellular (IHCL) and intramyocellular lipids were measured by 1H magnetic resonance spectroscopy. Hepatic and whole-body insulin sensitivity was assessed with a two-step hyperinsulinemic-euglycemic clamp (0.3 and 1.0 mU.kg-1.min-1). Findings HF and HFHP short-term diets, as well as an acute hyperlipidemic oral load, did not significantly change PCSK9 concentrations. In addition, post-prandial plasma triglyceride excursion was not altered in two carriers of PCSK9 LOF mutation compared with non carriers. In contrast, hypercaloric 7-day HFruc1 diet increased plasma PCSK9 concentrations by 28% (p=0.05) in healthy volunteers and by 34% (p=0.001) in OffT2D patients. In another independent study, 6-day HFruc2 diet increased plasma PCSK9 levels by 93% (p Conclusions Plasma PCSK9 concentrations vary minimally in response to a short term high-fat diet and they are not accompanied with changes in cholesterolemia upon high-fructose diet. Short-term high-fructose intake increased plasma PCSK9 levels, independent on cholesterol synthesis, suggesting a regulation independent of SREBP-2. Upon this diet, PCSK9 is associated with insulin resistance, hepatic steatosis and plasma triglycerides.

Published
2013
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3. Fasting plasma chenodeoxycholic acid and cholic acid concentrations are inversely correlated with insulin sensitivity in adults

Author

Laville Martine, Guyomarc'h-Delasalle Béatrice, Disse Emmanuel, Pouteau Etienne, Zaïr Yassine, Chetiveaux Maud, Cariou Bertrand, and Krempf Michel

Subjects
bile acids, insulin resistance, type 2 diabetes, FXR, TGR5, energy expenditure, hyperinsulinemic-euglycemic clamp, Nutrition. Foods and food supply, TX341-641, Nutritional diseases. Deficiency diseases, RC620-627
Abstract

Abstract Background Accumulating data suggest a novel role for bile acids (BAs) in modulating metabolic homeostasis. BA treatment has been shown to improve glucose tolerance and to increase energy expenditure in mice. Here, we investigated the relationship between fasting plasma BAs concentrations and metabolic parameters in humans. Findings Fasting plasma glucose, insulin and lipid profile were measured in 14 healthy volunteers, 20 patients with type 2 diabetes (T2D), and 22 non-diabetic abdominally obese subjects. Insulin sensitivity was also assessed by the determination of the glucose infusion rate (GIR) during a hyperinsulinemic-euglycemic clamp in a subgroup of patients (9 healthy and 16 T2D subjects). Energy expenditure was measured by indirect calorimetry. Plasma cholic acid (CA), chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) concentrations were analyzed by gas chromatograph-mass spectrometry. In univariable analysis, a positive association was found between HOMA-IR and plasma CDCA (β = 0.09, p = 0.001), CA (β = 0.03, p = 0.09) and DCA concentrations (β = 0.07, p < 0.0001). Spearman analysis retrieved an inverse relationship between plasma CDCA (r = -0.44, p = 0.03), CA (r = -0.65, p = 0.001) and the GIR. HOMA-IR remained positively associated with CDCA (β = 0.11, p = 0.01), CA (β = 0.04, p = 0.01) and DCA (β = 0.06, p = 0.007) in multivariable analysis, after adjustment for age, gender, BMI, HbA1C and plasma lipid parameters. In contrast, HbA1c, energy expenditure and plasma lipid concentrations were not correlated with plasma BAs levels in multivariable analysis. Conclusions Both plasma CDCA, CA and DCA concentrations were negatively associated with insulin sensitivity in a wide range of subjects.

Published
2011
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4. Integrated omics approach for the identification of HDL structure-function relationships in PCSK9-related familial hypercholesterolemia

Author

Darabi, Maryam, Lhomme, Marie, Ponnaiah, Maharajah, Pučić-Baković, Maja, Guillas, Isabelle, Frisdal, Eric, Bittar, Randa, Croyal, Mikaël, Matheron-Duriez, Lucrèce, Poupel, Lucie, Bonnefont-Rousselot, Dominique, Frere, Corinne, Varret, Mathilde, Krempf, Michel, Cariou, Bertrand, Lauc, Gordan, Guerin, Maryse, Carrie, Alain, Bruckert, Eric, Giral, Philippe, Le Goff, Wilfried, and Kontush, Anatol

Published
2023
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5. Cholesterol lowering effect of a soy drink enriched with plant sterols in a French population with moderate hypercholesterolemia

Author

Bard Jean-Marie, Krempf Michel, Weidner Christina, Cazaubiel Murielle, and Bell Doris

Subjects
Nutritional diseases. Deficiency diseases, RC620-627
Abstract

Abstract Background Plant sterols are an established non-pharmacological means to reduce total and LDL blood cholesterol concentrations and are therefore recommended for cholesterol management by worldwide-renown health care institutions. Their efficacy has been proven in many types of foods with the majority of trials conducted in spreads or dairy products. As an alternative to dairy products, soy based foods are common throughout the world. Yet, there is little evidence supporting the efficacy of plant sterols in soy-based foods. The objective of this study was to investigate the effect of a soy drink enriched with plant sterols on blood lipid profiles in moderately hypercholesterolemic subjects. Methods In a randomized, placebo-controlled double-blind mono-centric study, 50 subjects were assigned to 200 ml of soy drink either enriched with 2.6 g plant sterol esters (1.6 g/d free plant sterol equivalents) or without plant sterols (control) for 8 weeks. Subjects were instructed to maintain stable diet pattern and physical activity. Plasma concentrations of lipids were measured at initial visit, after 4 weeks and after 8 weeks. The primary measurement was the change in LDL cholesterol (LDL-C). Secondary measurements were changes in total cholesterol (TC), non-HDL cholesterol (non-HDL-C), HDL cholesterol (HDL-C) and triglycerides. Results Regular consumption of the soy drink enriched with plant sterols for 8 weeks significantly reduced LDL- C by 0.29 mmol/l or 7% compared to baseline (p < 0.05). TC and non-HDL-C concentrations decreased by 0.26 mmol/l and 0.31 mmol/l (each p < 0.05), respectively. Mean reductions in total, LDL and non-HDL cholesterol were significantly greater than in the placebo group (p < 0.05). HDL-C and triglycerides were not affected. Compliance was very high (>96%), and products were well tolerated. Conclusion Daily consumption of a plant sterol-enriched soy drink significantly decreased total, non-HDL and LDL cholesterol and is therefore an interesting and convenient aid in managing mild to moderate hypercholesterolemia.

Published
2008
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6. Burden of cardiovascular disease in a large contemporary cohort of patients with heterozygous familial hypercholesterolemia

Author

Angoulvant, Denis, Aouchiche, Karine, Beliard, Sophie, Boccara, Franck, Bruckert, Eric, Cariou, Bertrand, Carreau, Valérie, Carrie, Alain, Charrieres, Sybil, Cottin, Yves, Di Filippo, Mathilde, Dourmap, Caroline, Ducluzeau, Pierre-Henri, Durlach, Vincent, Farnier, Michel, Ferrari, Emile, Ferrieres, Dorota, Ferrieres, Jean, Gallo, Antonio, Hankard, Regis, Inamo, Jocelyn, Kalmykova, Olga, Krempf, Michel, Lemale, Julie, Moulin, Philippe, Paillard, François, Peretti, Noel, Perrin, Agnes, Pradignac, Alain, Pucheu, Yann, Rabes, Jean Pierre, Reynaud, Rachel, Rigalleau, Vincent, Schiele, François, Sultan, Ariane, Tounian, Patrick, Valero, René, Verges, Bruno, Yelnik, Cecile, Ziegler, Olivier, Ferrières, Jean, Vimont, Alexandre, Ferrières, Dorota, and Béliard, Sophie

Published
2022
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8. Sphingolipid and Trimethylamine-N-Oxide (TMAO) Levels in Women with Obesity after Combined Physical Training.

Author

Brandao, Camila Fernanda Cunha, Krempf, Michel, Giolo de Carvalho, Flávia, Aguesse, Audrey, Junqueira-Franco, Márcia Varella Morandi, Batitucci, Gabriela, de Freitas, Ellen Cristini, Noronha, Natalia Yumi, Rodrigues, Guilherme da Silva, Junqueira, Gizela Pedroso, Borba, Diego Alcantara, Billon-Crossouard, Stéphanie, Croyal, Mikael, and Marchini, Julio Sergio

Subjects
BODY composition, PHYSICAL fitness, OBESITY in women, PHYSICAL mobility, PHYSICAL training & conditioning, WEIGHT loss, ANAEROBIC threshold
Abstract

Obesity causes metabolic changes, such as the development of cardiovascular diseases. Moreover, physical exercise promotes protection against these diseases. Thus, the objective of the present study was to evaluate whether combined physical training can improve the metabolic system of women with obesity, reducing plasma concentrations of trimethylamine N-oxide (TMAO) and sphingolipids, regardless of weight loss. Fourteen obese women (BMI 30–40 kg/m2), aged 20–40 years, sedentary, were submitted to 8 weeks of combined physical training (strength and aerobic exercises). The training was performed three times/week, 55 min/session, at 75–90% maximum heart rate. All participants were evaluated pre- and post-exercise intervention, and their body composition, plasma TMAO, creatinine, lipid profile, and sphingolipid concentrations were recorded. Maximum oxygen consumption (VO2max), Speed lactate threshold 1 (SpeedLT1), and Speed lactate threshold 2 (SpeedLT2) evaluated physical performance. Results: After combined exercise, it did not change body composition, but TMAO, total cholesterol, and sphingolipid concentrations significantly decreased (p < 0.05). There was an increase in physical performance by improving VO2max, SpeedLT1, and SpeedLT2 (p < 0.05). The combined physical exercise could induce cardiovascular risk protection by decreasing TMAO in obese women, parallel to physical performance improvement, independent of weight loss. [ABSTRACT FROM AUTHOR]

Published
2024
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9. The Added Value of Coronary Calcium Score in Predicting Cardiovascular Events in Familial Hypercholesterolemia

Author

Angoulvant, Denis, Beliard, Sophie, Boccara, Franck, Bruckert, Eric, Cariou, Bertrand, Carreau, Valérie, Carrie, Alain, Charrieres, Sybil, Cottin, Yves, Di Filippo, Mathilde, Ducluzeau, Pierre Henri, Dulong, Sonia, Durlach, Vincent, Farnier, Michel, Ferrari, Emile, Ferrieres, Dorota, Ferrieres, Jean, Gallo, Antonio, Giral, Philippe, Gonbert, Sophie, Hankard, Regis, Inamo, Jocelyn, Kalmykova, Olga, Krempf, Michel, Lemale, Julie, Moulin, Philippe, Paillard, François, Peretti, Noel, Perrin, Agnes, Pradignac, Alain, Rabes, Jean Pierre, Rigalleau, Vincent, Schiele, François, Sultan, Ariane, Tounian, Patrick, Valero, René, Verges, Bruno, Yelnik, Cecile, Ziegler, Olivier, Aguado, Rocío, Alonso, Rodrigo, Álvarez-Baños, M<ce:sup loc='post">a</ce:sup> Pilar, Argüeso, Rosa, Arrieta, Francisco, Barba, Miguel Ángel, Casañas, Marta, Cepeda, José María, De Andrés, Raimundo, Díaz-Soto, Gonzalo, Díaz-Diaz, Jose Luis, Dieguez, Marta, Faedo, Ceferino, Fuentes, Francisco, Garrido, Juan A., González, Aurora, González-Bustos, Pablo, Mañas, M<ce:sup loc='post">a</ce:sup> Dolores, Mata, Pedro, Mauri, Marta, Mediavilla, Juan Diego, Michán, Alfredo, Miramontes, Pablo, Muñiz, Ovidio, Pérez, Leire, De Isla, Leopoldo Perez, Pintó, Xavier, Romero, Manuel J., Rubio, Patricia, Sánchez Muñoz-Torrero, Juan F., Vidal-Pardo, Jose I., Zambón, Daniel, Pérez de Isla, Leopoldo, Charrière, Sybil, Vimont, Alexandre, Muñiz-Grijalvo, Ovidio, Díaz-Díaz, José L., and Béliard, Sophie

Published
2021
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10. Large-scale screening of lipase acid deficiency in at risk population

Author

Tebani, Abdellah, Sudrié-Arnaud, Bénédicte, Boudabous, Hela, Brassier, Anais, Anty, Rodolphe, Snanoudj, Sarah, Abergel, Armand, Abi Warde, Marie-Thérèse, Bardou-Jacquet, Edouard, Belbouab, Reda, Blanchet, Eloi, Borderon, Corinne, Bronowicki, Jean-Pierre, Cariou, Bertrand, Carette, Claire, Dabbas, Myriam, Dranguet, Hélène, de Ledinghen, Victor, Ferrières, Jean, Guillaume, Maeva, Krempf, Michel, Lacaille, Florence, Larrey, Dominique, Leroy, Vincent, Musikas, Marietta, Nguyen-Khac, Eric, Ouzan, Denis, Perarnau, Jean-Marc, Pilon, Carine, Ratzlu, Vlad, Thebaut, Alice, Thevenot, Thierry, Tragin, Isabelle, Triolo, Valérie, Vergès, Bruno, Vergnaud, Sabrina, and Bekri, Soumeya

Published
2021
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11. Efficacy and safety of volanesorsen in patients with multifactorial chylomicronaemia (COMPASS): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial

Author

Agarwal, Abhay, Ballantyne, Christie, Baum, Seth, Bergeron, Jean, Bruckert, Eric, Burdick, Richard, Castro-Cabezas, Manuel, Cervi, Mark, Corder, Clinton, DuFour, Robert, Farrington, Cecil Murray, Francis, Gordon, Galitz, Lawrence, Hamstead, Steven, Hemphill, Linda, Huffman, Cynthia, Issa, Basil, Julius, Ulrich, Kane, John, Krempf, Michel, Martin, Steven, Powell, James, Shultzaberger, Richard, Thompson, Craig, Thompson-Hargrave, Letitia, Toth, Peter, Turner, Traci, Valero, Rene, Verges, Bruno, Visseren, Frank L J, Vyas, Pankaj, Yataco, Alberto, Gouni-Berthold, Ioanna, Alexander, Veronica J, Yang, Qingqing, Hurh, Eunju, Steinhagen-Thiessen, Elisabeth, Moriarty, Patrick M, Hughes, Stephen G, Gaudet, Daniel, Hegele, Robert A, O'Dea, Louis St L, Stroes, Erik S G, Tsimikas, Sotirios, and Witztum, Joseph L

Published
2021
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12. SAFEHEART risk-equation and cholesterol-year-score are powerful predictors of cardiovascular events in French patients with familial hypercholesterolemia

Author

Angoulvant, Denis, Beliard, Sophie, Boccara, Franck, Bruckert, Eric, Cariou, Bertrand, Carreau, Valérie, Carrie, Alain, Charriere, Sybil, Cottin, Yves, Filippo, Mathilde DI., Dulong, Sonia, Durlach, Vincent, Farnier, Michel, Ferrari, Emile, Ferrieres, Dorota, Ferrieres, Jean, Gallo, Antonio, Giral, Philippe, Gonbert, Sophie, Hankard, Regis, Inamo, Jocelyn, Kalmykova, Olga, Krempf, Michel, Moulin, Philippe, Paillard, François, Peretti, Noel, Perrin, Agnes, Pierre Rabes, Jean, Sultan, Ariane, Tounian, Patrick, Valero, René, Verges, Bruno, Yelnik, Cecile, Ziegler, Olivier, Vimont, Alexandre, Chapman, M. John, Carrié, Alain, and Béliard, Sophie

Published
2020
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16. Residual vascular risk in diabetes – Will the SPPARM alpha concept hold the key?

Author

Fruchart, Jean-Charles, Santos, Raul D., Yamashita, Shizuya, Aikawa, Masanori, Libby, Peter, Plutzky, Jorge, Pradhan, Aruna, Ridker, Paul, Aguilar-Salinas, Carlos, Al Rasadi, Khalid, Amarenco, Pierre, Barter, Philip J., Ceska, Richard, Corsini, Alberto, Ruscica, Massimiliano, Després, Jean-Pierre, Duriez, Patrick, Eckel, Robert H., Ezhov, Marat V., Farnier, Michel, Ginsberg, Henry N., Hermans, Michel P., Ishibashi, Shun, Karpe, Fredrik, Kodama, Tatsuhiko, Koenig, Wolfgang, Krempf, Michel, Lim, Soo, Lorenzatti, Alberto J., McPherson, Ruth, Nuñez-Cortes, Jesus Millan, Nordestgaard, Børge G., Ogawa, Hisao, Packard, Chris J., Ponte-Negretti, Carlos I., Reiner, Željko, Sadikot, Shaukat, Shimano, Hitoshi, Sritara, Piyamitr, Stock, Jane K., Su, Ta-Chen, Susekov, Andrey V., Tartar, André, Taskinen, Marja-Riitta, Tenenbaum, Alexander, Tokgözoğlu, Lale S., Tomlinson, Brian, Tybjærg-Hansen, Anne, Valensi, Paul, Vrablík, Michal, Wahli, Walter, Watts, Gerald F., Yokote, Koutaro, and Zambon, Alberto

Published
2019
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23. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Author

Hamann, Andreas, Barakat, Alain, Blüher, Matthias, Linn, Thomas, Mölle, Andrea, Segner, Alexander, Stübler, Petra, Tosch-Sisting, Regina, Pacini, Furio, Santini, Ferruccio, Marchesini, Giulio, Rotella, Carlo Maria, Invitti, Cecilia, Vettor, Roberto, Buscemi, Silvio, Raya, Pedro Mezquita, Freijoo, Felipe Casanueva, de Barbará, Ramón Gomis, Carraro, Raffaele, Bobillo, Enrique Romero, de la Cuesta, Carmen, Farsang, Csaba, Csaszar, Albert, Zahorska-Markiewicz, Barbara, Pupek-Musialik, Danuta, Franek, Edward, Ostrowska, Lucyna, Olszanecka-Glinianowicz, Magdalena, Lalic, Nebojsa, Micic, Dragan, Ludvik, Bernhard, Paulweber, Bernhard, Prager, Rudolf, Scheen, André, Van Gaal, Luc, Astrup, Arne Vernon, Hermansen, Kjeld, Madsbad, Sten, Rissanen, Aila, Nieminen, Sakari, Savolainen, Markku, Krempf, Michel, Romon, Monique, Laville, Martine, Marre, Michel, Mira, Reginald, Finucane, Francis, Veenendaal, Aletha, van Berkum, Frank, Johannsson-Vidarsdóttir, Solrun, Van de Walle, Vivienne, Meesters, Eelco, Hjelmesæth, Jøran, Klemsdal, Tor Ole, Kulseng, Bård, Bach-Kliegel, Birgit, Laederach, Kurt, Villiger, Lukas, Golay, Alain, Bilz, Stefan, Sathyapalan, Thozhukat, Bain, Stephen, Kumar, Sudesh, Le Roux, Carel Wynard, Lean, Michael E.J., McGowan, Barbara, Rehman, Tariq, Wilding, John, Wittert, Gary, Caterson, Ian, Proietto, Joeseph, Prins, John, Neto, Bruno Geloneze, Gross, Jorge Luiz, Chacra, Antonio Roberto, Halpern, Alfredo, de Almeida Suplicy, Henrique, Chow, Francis Chun Chung, Thacker, Hemant P, Chadha, Manoj, Chandalia, Hemaraj, Unnikrishnan, Ambika, Kalra, Sanjay, Deshpande, Neeta, Shunmugavelu, Minakshi, Deshmukh, Vaishali Chetan, Maislos, Maximo, Lieberman, Gabriella Segal, Shimon, Ilan, Stern, Naftali, Nabriski, Dan, Karnieli, Eddy, Shehadeh, Naim, Gonzalez-Galvez, Guillermo, del Rosario Arechavaleta-Granell, Maria, Ortiz, Rafael Margarito Violante, Franco, Guadalupe Morales, Gurieva, Irina, Suplotova, Lyudmila Aleksandrovna, Troshina, Ekaterina, Ruyatkina, Ludmila Aleksandrovna, Voychik, Emma Anatolievna, Martsevich, Sergey, Startseva, Maria A, Seeber, Mary Elizabeth, Badat, Aysha, Ellis, Graham, Altuntas, Yuksel, Guler, Serdar, Ulgen, Ender, Delibasi, Tuncay, Chetty, Tony, Hart, Randy, Janzen, Jeannette, Labonte, Isabelle, Lau, David, Liutkus, Joanne, O'Keefe, Dennis, Padwal, Raj, Ransom, Thomas P.P., Tytus, Richard, Weisnagel, Stanley John, Adler, Jay, Aqua, Keith, Aronoff, Stephen L, Bedel, Gary W., Blevins, Thomas Craig, Blumenau, Joe, Brockmyre, Andrew Peter, Call, Robert S, Canadas, Rafael, Chaykin, Louis B, Cohen, Kenneth, Conrow, Jeffrey Keith, Davis, Matthew G, Downey, H Jackson, Drosman, Steven Richard, Duckor, Steven, Farmer, H. Frank, Farrell, James, Fehnel, Stephen, Finneran, Matthew Patrick, Forbes, Ray, Forker, Alan, Fredrick, Mark, Fujioka, Ken, Geller, Steven Andrew, Gill, Santosh, Glaser, Linda, Greco, Susan Neims, Greenway, Frank Lyons, Harper, Wayne, Herman, Lee, Hoekstra, John, Ingebretsen, Richard, Ison, Rodney, Jain, Rajeev K, Kaplan, Roy, Kaster, Steven Richard, Haase, Gregory A, Kerzner, Boris, Kirstein, Judith Lee, Koltun, William, Krieger, Diane R, Lewis, Cora Elizabeth, Madder, Robert, Marple, Richard N, McDermott, Edward J, Mello, Curtis John, Miller, Alan B., Mullen, Julie, Nardandrea, John, O'Neil, Patrick, Pi-Sunyer, F. Xavier, Pucillo, Ronald M, Rhee, Chanhaeng, Redrick, Scott, Pardini, Aaron, Rothman, Jeffrey, Rubino, Domenica Marie, Sellers, Gladstone, Smith, Timothy, Byars, William David, Soufer, Joseph, Sussman, Allen Michael, Patrick, Kyle, Schramm, Erich Lloyd, Van Cleeff, Martin, Berg, Saul Reuel, Wyatt, Holly Roxanna, Simon, James Alan, le Roux, Carel W, Astrup, Arne, Greenway, Frank, Lau, David C W, Ortiz, Rafael Violante, Wilding, John P H, Skjøth, Trine V, Manning, Linda Shapiro, and Pi-Sunyer, Xavier

Published
2017
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49. PCSK9 and LDL cholesterol: unravelling the target to design the bullet

Author

Costet, Philippe, Krempf, Michel, and Cariou, Bertrand

Subjects
Hypercholesterolemia -- Health aspects, Human genetics -- Research, Biological sciences, Chemistry
Abstract

Gain-of-function mutations within proprotein convertase subtilisin kexin type 9 (PCSK9) are linked to familial autosomal dominant hypercholesterolaemia, a disease characterized by elevated plasma concentrations of cholesterol associated with low-density lipoproteins (LDLs). Conversely, PCSK9 loss-of-function mutations result in low levels of LDL cholesterol (LDLC) and protect against coronary heart disease. Although compelling evidence indicates that PCSK9 impairs the LDLR pathway, its role in cholesterol metabolism remains incompletely defined. In the past two years, several new biochemical findings, including the PCSK9 crystal structure and the identification of several transcriptional repressors, were reported. Moreover, new clinical and epidemiological data have revealed the correlation between plasma PCSK9 concentrations and LDLC levels.

Published
2008

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