scholarly journals Gene Therapy Targeting PCSK9

Metabolites ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 70
Author(s):  
Julius L. Katzmann ◽  
Arjen J. Cupido ◽  
Ulrich Laufs
Keyword(s):  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cardiovascular Prevention ◽  
Single Nucleotide ◽  
Pcsk9 Gene ◽  
Current State ◽  
Interfering Rna

The last decades of research in cardiovascular prevention have been characterized by successful bench-to-bedside developments for the treatment of low-density lipoprotein (LDL) hypercholesterolemia. Recent examples include the inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) with monoclonal antibodies, small interfering RNA and antisense RNA drugs. The cumulative effects of LDL cholesterol on atherosclerosis make early, potent, and long-term reductions in LDL cholesterol desirable—ideally without the need of regular intake or application of medication and importantly, without side effects. Current reports show durable LDL cholesterol reductions in primates following one single treatment with PCSK9 gene or base editors. Use of the CRISPR/Cas system enables precise genome editing down to single-nucleotide changes. Provided safety and documentation of a reduction in cardiovascular events, this novel technique has the potential to fundamentally change our current concepts of cardiovascular prevention. In this review, the application of the CRISPR/Cas system is explained and the current state of in vivo approaches of PCSK9 editing is presented.

scholarly journals Statin-induced myopathy – a challenge for patients and physicians

2021 ◽  
Vol 16 (2) ◽  
pp. 148-152
Author(s):  
Gabriela Anca ANGELESCU ◽  
◽  
Mirela Marioara TOMA ◽  
Valentin VARLAS ◽  
◽  
...  
Keyword(s):  
Clinical Trials ◽  
Creatine Kinase ◽  
Side Effect ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Treatment Strategies ◽  
Density Lipoprotein ◽  
Review Article ◽  
Low Density

Statins are the most frequently used drugs for lowering the low density lipoprotein (LDL)-cholesterol and are proven to decrease the cardiovascular-driven mortality. The statin-induced myopathy represents a side effect of the statin therapy and includes heterogenous muscular symptoms, associated with an increase in the creatine kinase (CK) levels, according to clinical trials, at an incidence of 1.5-5%. The statin-induced myopathy is challenging for clinicians, in order to maintain the specific therapeutic approach for each case, as well as for patients at a high risk of cardiovascular diseases, who acknowledges the long-term benefits of the treatment. The aim of this review article is to showcase the types of statin-induced myopathy, the patient cohorts susceptible of developing this side effect and the treatment strategies for hypercholesterolemia/ dyslipidemia.

Drug-induced dyslipoproteinemia: a report of two cases.

1980 ◽  
Vol 26 (1) ◽  
pp. 163-168
Author(s):  
H K Naito ◽  
M C McHenry ◽  
L A Lewis
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Lipoproteins ◽  
Drug Induced ◽  
Drug Induction ◽  
Secondary Form ◽  
Species Specific

Abstract We describe two cases of atypical dyslipoproteinemia due to drug-induction. This secondary form of lipoprotein abnormality is unique because the newly available drug, miconazole, apparently directly delipidated the alpha-lipoproteins in the bloodstream. On closer study we found that the delipidation was caused by the vehicle rather than the fungicide--more specifically, only by the polyethoxylated castor oil in the vehicle. It affects serum lipoproteins both in vitro and in vivo, and the effect is species-specific. In vitro studies indicate that it preferentially delipidates high-density lipoprotein rather than low-density lipoprotein. Because its effects on the serum lipoproteins of rats resemble those on man, and because aortic lesions were produced in rats injected daily (90 mL/L) with this substance, caution is indicated in long-term use of drugs containing this chemical component in the vehicle.

Personalized medicine in lipid-modifying therapy

2021 ◽  
Vol 18 (2) ◽  
pp. 185-203
Author(s):  
Brian Tomlinson ◽  
Chen-Hsiu Lin ◽  
Paul Chan ◽  
Christopher WK Lam
Keyword(s):  
Genetic Factors ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Low Density Lipoprotein Cholesterol ◽  
First Line ◽  
Absolute Level ◽  
Interfering Rna

The choice of lipid-modifying treatment is largely based on the absolute level of cardiovascular risk and baseline lipid profile. Statins are the first-line treatment for most patients requiring reduction of low-density-lipoprotein cholesterol (LDL-C) and ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors can be added to reach LDL-C targets. Statins have some adverse effects that are somewhat predictable based on phenotypic and genetic factors. Fibrates or omega-3 fatty acids can be added if triglyceride levels remain elevated. The RNA-targeted therapeutics in development offer the possibility of selective liver targeting for specific lipoproteins such as lipoprotein(a) and long-term reduction of LDL-C with infrequent administration of a small-interfering RNA may help to overcome the problem of adherence to therapy.

Identification of the hemangioblast in postnatal life

Blood ◽  
2002 ◽  
Vol 100 (9) ◽  
pp. 3203-3208 ◽  
Author(s):  
Elvira Pelosi ◽  
Mauro Valtieri ◽  
Simona Coppola ◽  
Rosanna Botta ◽  
Marco Gabbianelli ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Low Density Lipoprotein ◽  
Cell Subset ◽  
Growth Factor Receptor ◽  
Density Lipoprotein ◽  
Postnatal Life ◽  
Proliferative Potential

Abstract Postnatal CD34+ cells expressing vascular endothelial growth factor receptor 2 (KDR) generate hematopoietic or endothelial progeny in different in vitro and in vivo assays. Hypothetically, CD34+KDR+ cells may comprise hemangioblasts bipotent for both lineages. This hypothesis is consistent with 2 series of experiments. In the first series, in clonogenic culture permissive for hematopoietic and endothelial cell growth, CD34+KDR+ cells generate large hemato-endothelial (Hem-End) colonies (5% of seeded cells), whereas CD34+KDR− cells do not. Limiting-dilution analysis indicates that Hem-End colonies are clonally generated by single hemangioblasts. Sibling cells generated by a hemangioblast, replated in unicellular culture, produce either hematopoietic or Hem-End colonies, depending on the specific culture conditions. Identification of endothelial cells was based on the expression of VE-cadherin and endothelial markers and with lack of CD45 and hematopoietic molecules, as evaluated by immunofluorescence, immunocytochemistry, and reverse transcription–polymerase chain reaction. Furthermore, endothelial cells were functionally identified using low-density lipoprotein (LDL) uptake and tube-formation assays. In the second series, to evaluate the self-renewal capacity of hemangioblasts, single CD34+KDR+ cells were grown in 3-month extended long-term culture (ELTC) through 3 serial culture rounds—that is, blast cells generated in unicellular ELTC were reseeded for a subsequent round of unicellular ELTC. After 9 months, 10% blasts from tertiary ELTC functioned as hemangioblasts and generated macroscopic Hem-End colonies in clonogenic culture. These studies identified postnatal hemangioblasts in a CD34+KDR+ cell subset, endowed with long-term proliferative potential and bilineage differentiation capacity. Although exceedingly rare, hemangioblasts may represent the lifetime source/reservoir for primitive hematopoietic and endothelial progenitors.

Effect of a Long-Term Fat-Modified Diet on Serum Lipoprotein Levels of Cholesterol and Triglyceride in Patients on Home Haemodialysis

1981 ◽  
Vol 60 (1) ◽  
pp. 81-86 ◽  
Author(s):  
V. J. Wass ◽  
R. J. Jarrett ◽  
V. Meilton ◽  
M. K. Start ◽  
M. Mattock ◽  
...  
Keyword(s):  
Total Cholesterol ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Low Density ◽  
Home Haemodialysis ◽  
Cholesterol Levels ◽  
Modified Diet

1. Changes in serum total and lipoprotein fraction triglyceride and cholesterol levels were studied in 24 adults on home haemodialysis. Half the patients were randomly allocated to a low cholesterol (mean 200 mg/day), fat-modified diet (mean polyunsaturated/saturated fat ratio of 1.0 with a mean of 43% of the total energy content derived from fat). 2. Before dietary manipulation, triglyceride levels in all lipoprotein fractions were significantly higher (P < 0.02) than in a control group of age and sex matched normal subjects. Total cholesterol, very-low-density-lipoprotein (VLDL) and low-density-lipoprotein (LDL) cholesterol were also significantly raised (P < 0.02), but high-density-lipoprotein (HDL) cholesterol was normal. In the patients on a fat-modified diet triglyceride levels did not alter in any of the lipoprotein fractions. Total cholesterol and LDL cholesterol levels fell significantly into the normal range (P < 0.002 and < 0.001 respectively) but VLDL and HDL cholesterol levels did not change. 3. Hypertriglyceridaemia is the most common lipid abnormality in patients with renal failure and a long-term fat-modified diet is, therefore, of limited therapeutic importance in these patients unless there is a low HDL/LDL cholesterol ratio.

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