Colesterol e ictus: papel de los inhibidores de la proproteína convertasa subtilisina/kexina tipo 9 by L. Castilla-Guerra, M.C. Fernández-Moreno, M.A. Rico-Corral

“…PCSK9 binds to the LDL receptor (LDLR), disrupts its endocytic recycling itinerary and directs it to lysosomal degradation. …”
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Lipoprotein glomerulopathy associated with the Osaka/Kurashiki APOE variant: two cases identified in Latin America by Joaquim Nelito da Silveira-Neto, Guilherme Jinson de Oliveira Ahn, Precil Diego Miranda de Menezes Neves, Vinicius Augusto Ferreira Baptista, Stanley de Almeida Araújo, David Campos Wanderley, Andréia Watanabe, Elieser Hitoshi Watanabe, Neide Missae Murai, Eny Maria Goloni Bertollo, Osvaldo Merege Vieira-Neto, Márcio Dantas, Sergio Ricardo de Antônio, Roberto Silva Costa, Maria Alice Sperto Ferreira Baptista, Miguel Moysés-Neto, Luiz Fernando Onuchic

“…His apolipoprotein E serum level was 72 mg/dL and genetic analysis revealed the APOE pathogenic variant c.527G > C, p.Arg176Pro in heterozygosis, known as the Osaka/Kurashiki mutation and positioned nearby the LDL receptor binding site. Case 2 A 34-year-old Caucasian man sought medical assessment for renal dysfunction and hypertension. …”
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Beneficial impact of epigallocatechingallate on LDL-C through PCSK9/LDLR pathway by blocking HNF1α and activating FoxO3a by Chuan-Jue Cui, Jing-Lu Jin, Lin-Na Guo, Jing Sun, Na-Qiong Wu, Yuan-Lin Guo, Geng Liu, Qian Dong, Jian-Jun Li

“…In the high fat diet (HFD) fed rats, EGCG administration significantly lowered circulating PCSK9 concentration and liver PCSK9 expression, along with up-regulated LDL receptor (LDLR) expression but decreased level of LDL-C. …”
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Macrophage beta2-adrenergic receptor is dispensable for the adipose tissue inflammation and function by Kasparas Petkevicius, Guillaume Bidault, Sam Virtue, Stephen A. Newland, Martin Dale, Aurelien Dugourd, Julio Saez-Rodriguez, Ziad Mallat, Antonio Vidal-Puig

“…Finally, macrophage-specific B2AR deletion does not affect the development of atherosclerosis on an LDL receptor-null genetic background. Conclusions: Overall, our data suggest that the SNS does not directly modulate the phenotype of adipose tissue macrophages in either lean mice or mouse models of cardiometabolic disease. …”
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PCSK9 is not secreted from mature differentiated intestinal cells by Moreau François, Aurélie Thédrez, Damien Garçon, Audrey Ayer, Thibaud Sotin, Wieneke Dijk, Claire Blanchard, Gilliane Chadeuf, Lucie Arnaud, Mikael Croyal, Laurianne Van Landeghem, Melissa Touvron, Xavier Prieur, Anna Roubtsova, Nabil Seidah, Annik Prat, Bertrand Cariou, Cedric Le May

“…Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes lysosomal degradation of the LDL receptor and is a key regulator of cholesterol metabolism. …”
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Polygenic Markers in Patients Diagnosed of Autosomal Dominant Hypercholesterolemia in Catalonia: Distribution of Weighted LDL-c-Raising SNP Scores and Refinement of Variant Selecti... by Jesús M. Martín-Campos, Sheila Ruiz-Nogales, Daiana Ibarretxe, Emilio Ortega, Elisabet Sánchez-Pujol, Meritxell Royuela-Juncadella, Àlex Vila, Carolina Guerrero, Alberto Zamora, Cristina Soler i Ferrer, Juan Antonio Arroyo, Gemma Carreras, Susana Martínez-Figueroa, Rosa Roig, Núria Plana, Francisco Blanco-Vaca, Xarxa d’Unitats de Lípids i Arteriosclerosi (XULA)

“…Familial hypercholesterolemia (FH) is associated with mutations in the low-density lipoprotein (LDL) receptor (<i>LDLR</i>), apolipoprotein B (<i>APOB</i>), and proprotein convertase subtilisin/kexin 9 (<i>PCSK9</i>) genes. …”
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Assessing statin effects on cardiovascular pathways in HIV using a novel proteomics approach: Analysis of data from INTREPID, a randomized controlled trialResearch in context by Mabel Toribio, Kathleen V. Fitch, Lauren Stone, Markella V. Zanni, Janet Lo, Chris de Filippi, Craig A. Sponseller, Hang Lee, Ida Grundberg, Melanie A. Thompson, Judith A. Aberg, Steven K. Grinspoon

“…Among all participants, three proteins significantly decreased: tissue factor pathway inhibitor [TFPI; t-statistic = −6.38, FDR p-value<0.0001], paraoxonase 3 [PON3; t-statistic = −4.64, FDR p-value = 0.0003], and LDL-receptor [LDLR; t-statistic = −4.45, FDR p-value = 0.0004]; and two proteins significantly increased galectin-4 [Gal-4; t-statistic = 3.50, FDR p-value = 0.01] and insulin-like growth factor binding protein 2 [IGFBP-2; t-statistic = 3.21, FDR p-value = 0.03]. …”
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A novel approach to oral apoA-I mimetic therapy[S] by Arnab Chattopadhyay, Mohamad Navab, Greg Hough, Feng Gao, David Meriwether, Victor Grijalva, James R. Springstead, Mayakonda N. Palgnachari, Ryan Namiri-Kalantari, Feng Su, Brian J. Van Lenten, Alan C. Wagner, G.M. Anantharamaiah, Robin Farias-Eisner, Srinivasa T. Reddy, Alan M. Fogelman

“…EV or 6F tomatoes were harvested, lyophilized, ground into powder, added to Western diet (WD) at 2.2% by weight, and fed to LDL receptor-null (LDLR−/−) mice at 45 mg/kg/day 6F. …”
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Epigenomic profiling of non-small cell lung cancer xenografts uncover LRP12 DNA methylation as predictive biomarker for carboplatin resistance by Sabrina Grasse, Matthias Lienhard, Steffen Frese, Martin Kerick, Anne Steinbach, Christina Grimm, Michelle Hussong, Jana Rolff, Michael Becker, Felix Dreher, Uwe Schirmer, Stefan Boerno, Anna Ramisch, Gunda Leschber, Bernd Timmermann, Christian Grohé, Heike Lüders, Martin Vingron, Iduna Fichtner, Sebastian Klein, Margarete Odenthal, Reinhard Büttner, Hans Lehrach, Holger Sültmann, Ralf Herwig, Michal R. Schweiger

“…This analysis led to the identification of a promoter CpG island methylation of LDL receptor-related protein 12 (LRP12) associated with increased resistance to carboplatin. …”
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Deletion of NoxO1 limits atherosclerosis development in female mice by Giulia K. Buchmann, Christoph Schürmann, Tim Warwick, Marcel H. Schulz, Manuela Spaeth, Oliver J. Müller, Katrin Schröder, Hanjoong Jo, Norbert Weissmann, Ralf P. Brandes

“…Methods and results: Wildtype (WT) and NoxO1 knockout mice were treated with high fat diet and adeno-associated virus (AAV) overexpressing pro-protein convertase subtilisin/kexin type 9 (PCSK9) to induce hepatic low-density lipoprotein (LDL) receptor loss. As a result, massive hypercholesterolemia was induced and spontaneous atherosclerosis developed within three month. …”
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Smooth muscle liver kinase B1 inhibits foam cell formation and atherosclerosis via direct phosphorylation and activation of SIRT6 by Qiming Deng, Hongxuan Li, Xiaolin Yue, Chenghu Guo, Yuanyuan Sun, Chang Ma, Jiangang Gao, Yue Wu, Bin Du, Jianmin Yang, Cheng Zhang, Wencheng Zhang

“…Mechanistically, LKB1 binds to SIRT6 and directly phosphorylates and activates it, thereby reducing lectin-like oxLDL receptor-1 (LOX-1) via SIRT6-dependent histone deacetylation. …”
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High fat / high cholesterol diet does not provoke atherosclerosis in the ω3-and ω6-polyunsaturated fatty acid synthesis–inactivated Δ6-fatty acid desaturase–deficient mouse by Wilhelm Stoffel, Erika Binczek, Inga Schmidt-Soltau, Susanne Brodesser, Ina Wegner

“…Neither PUFA-free regular nor long-term HFHC-diet impacts the apoe- and LDL-receptor deficiency–provoked hypercholesterolemia and atherosclerotic plaque formation, size and distribution in the aorta. …”
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Transgenic 6F tomatoes act on the small intestine to prevent systemic inflammation and dyslipidemia caused by Western diet and intestinally derived lysophosphatidic acid[S] by Mohamad Navab, Greg Hough, Georgette M. Buga, Feng Su, Alan C. Wagner, David Meriwether, Arnab Chattopadhyay, Feng Gao, Victor Grijalva, Janet S. Danciger, Brian J. Van Lenten, Elin Org, Aldons J. Lusis, Calvin Pan, G.M. Anantharamaiah, Robin Farias-Eisner, Susan S. Smyth, Srinivasa T. Reddy, Alan M. Fogelman

“…We recently reported that levels of unsaturated lysophosphatidic acid (LPA) in the small intestine significantly correlated with the extent of aortic atherosclerosis in LDL receptor-null (LDLR−/−) mice fed a Western diet (WD). …”
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Human crypt intestinal epithelial cells are capable of lipid production, apolipoprotein synthesis, and lipoprotein assembly by Emile Levy, Jean-François Beaulieu, Edgard Delvin, Ernest Seidman, Wagner Yotov, Jean-René Basque, Daniel Ménard

“…HIEC demonstrated both endogenous cholesterol synthesis and LDL receptor expression. Cholesterol synthesis was sensitive to 25-hydroxycholesterol and mevinolin, but unresponsive to LDL treatment, suggesting independent regulation pathways. …”
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Differential Effect of Dietary Supplementation with a Soybean Oil Enriched in Oleic Acid versus Linoleic Acid on Plasma Lipids and Atherosclerosis in LDLR-Deficient Mice by Zhi-Hong Yang, Kimball Nill, Yuki Takechi-Haraya, Martin P. Playford, David Nguyen, Zu-Xi Yu, Milton Pryor, Jingrong Tang, Krishna Vamsi Rojulpote, Nehal N. Mehta, Han Wen, Alan T. Remaley

“…To test whether diets rich in CSO versus MSO would attenuate atherosclerosis development, LDL receptor knock-out (LDLR-KO) mice were fed a Western diet enriched in saturated fatty acids (control), or a Western diet supplemented with 5% (<i>w</i>/<i>w</i>) LA-rich CSO or high-oleic MSO for 12 weeks. …”
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The steroidal analog GW707 activates the SREBP pathway through disruption of intracellular cholesterol trafficking by Jessie Zhang, Nicole Dudley-Rucker, Jan R. Crowley, Elvira Lopez-Perez, Marc Issandou, Jean E. Schaffer, Daniel S. Ory

“…Recently, a new class of lipid-lowering agents has been described that upregulate LDL receptor (LDLr) activity. These agents are proposed to activate sterol-regulated gene expression through binding to the sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP). …”
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Reducing Premature Coronary Artery Disease in Malaysia by Early Identification of Familial Hypercholesterolemia Using the Familial Hypercholesterolemia Case Ascertainment Tool (FAM... by Anis Safura Ramli, Nadeem Qureshi, Hasidah Abdul-Hamid, Aisyah Kamal, Johanes Dedi Kanchau, Nur Syahirah Shahuri, Ralph Kwame Akyea, Luisa Silva, Laura Condon, Suraya Abdul-Razak, Alyaa Al-Khateeb, Yung-An Chua, Mohamed-Syarif Mohamed-Yassin, Noorhida Baharudin, Siti Fatimah Badlishah-Sham, Aznida Firzah Abdul Aziz, Noor Alicezah Mohd Kasim, Siti Hamimah Sheikh Abdul Kadir, Joe Kai, Jo Leonardi-Bee, Hapizah Nawawi

“… BackgroundFamilial hypercholesterolemia (FH) is predominantly caused by mutations in the 4 FH candidate genes (FHCGs), namely, low-density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB-100), proprotein convertase subtilisin/kexin type 9 (PCSK9), and the LDL receptor adaptor protein 1 (LDLRAP1). It is characterized by elevated low-density lipoprotein cholesterol (LDL-c) levels leading to premature coronary artery disease. …”
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Compound Danshen Dripping Pill inhibits hypercholesterolemia/atherosclerosis-induced heart failure in ApoE and LDLR dual deficient mice via multiple mechanisms by Yanfang Yang, Ke Feng, Liying Yuan, Yuxin Liu, Mengying Zhang, Kaimin Guo, Zequn Yin, Wenjia Wang, Shuiping Zhou, He Sun, Kaijing Yan, Xijun Yan, Xuerui Wang, Yajun Duan, Yunhui Hu, Jihong Han

“…We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE–/–LDLR–/–) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. …”
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NOTCH1 mutation associates with impaired immune response and decreased relapse-free survival in patients with resected T1-2N0 laryngeal cancer by Xiao-yang Gong, Hai-bin Chen, Li-qing Zhang, Dong-sheng Chen, Wang Li, Dong-hui Chen, Jin Xu, Han Zhou, Le-le Zhao, Yun-jie Song, Ming-zhe Xiao, Wang-long Deng, Chuang Qi, Xue-rong Wang, Xi Chen

“…A total of 469 genomic alterations were detected in 211 distinct cancer-relevant genes, and the genes found to be mutated in more than five patients (&gt;10%) included tumor protein p53 (TP53, 78.5%), FAT atypical cadherin 1 (FAT1, 26%), LDL receptor related protein 1B (LRP1B, 19%), cyclin dependent kinase inhibitor 2A (CDKN2A, 17%), tet methylcytosine dioxygenase 2 (TET2, 17%), notch receptor 1 (NOTCH1, 12%) and neuregulin 1 (NRG1, 12%). …”
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Anacetrapib reduces (V)LDL cholesterol by inhibition of CETP activity and reduction of plasma PCSK9[S] by Sam J.L. van der Tuin, Susan Kühnast, Jimmy F.P. Berbée, Lars Verschuren, Elsbet J. Pieterman, Louis M. Havekes, José W.A. van der Hoorn, Patrick C.N. Rensen, J. Wouter Jukema, Hans M.G. Princen, Ko Willems van Dijk, Yanan Wang

“…We found that hepatic proprotein convertase subtilisin/kexin type 9 (Pcsk9) expression was decreased (−28%, P < 0.01), accompanied by decreased plasma PCSK9 levels (−47%, P < 0.001) and increased hepatic LDL receptor (LDLr) content (+64%, P < 0.01). Consistent with this, anacetrapib increased the clearance and hepatic uptake (+25%, P < 0.001) of [14C]cholesteryl oleate-labeled VLDL-mimicking particles. …”
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