scholarly journals Novel RNAi-Based Therapies for Atherosclerosis

2021 ◽  
Vol 23 (8) ◽  
Author(s):  
Anna-Kaisa Ruotsalainen ◽  
Petri Mäkinen ◽  
Seppo Ylä-Herttuala
Keyword(s):  
Plasma Cholesterol ◽  
Common Factor ◽  
New Drugs ◽  
Blood Cholesterol ◽  
Advanced Treatment ◽  
Cell Debris ◽  
Cholesterol Levels ◽  
Atherosclerosis Risk ◽  
Artery Disease ◽  
Atherosclerosis Risk Factors

Abstract Purpose of Review Atherosclerosis, defined by inflammation and accumulation of cholesterol, extracellular matrix, and cell debris into the arteries is a common factor behind cardiovascular diseases (CVD), such as coronary artery disease, peripheral artery disease, and stroke. In this review, we discuss and describe novel RNA interference (RNAi)-based therapies in clinical trials and on the market. Recent Findings The first RNAi-based therapies have entered clinical use for the control of atherosclerosis risk factors, i.e., blood cholesterol levels. The most advanced treatment is silencing of proprotein convertase subtilisin/kexin type 9 (PCSK9) with a drug called inclisiran, which has been approved for the treatment of hypercholesterolemia in late 2020, and results in a robust decrease in plasma cholesterol levels. Summary As the new RNAi therapies for atherosclerosis are now entering markets, the usefulness of these therapies will be further evaluated in larger patient cohorts. Thus, it remains to be seen how fast, effectively and eminently these new drugs consolidate their niche within the cardiovascular disease drug palette.

Risk Factors for Coronary Artery Disease in Children: Recognition, Evaluation, and Therapy

1980 ◽  
Vol 2 (5) ◽  
pp. 131-138
Author(s):  
C. J. Glueck ◽  
M. J. Mellies ◽  
R. C. Tsang ◽  
J. A. Morrison
Keyword(s):  
Risk Factors ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Eating Habits ◽  
Plasma Cholesterol ◽  
Saturated Fat ◽  
Cholesterol Levels ◽  
Chd Risk ◽  
Artery Disease ◽  
Atherosclerosis Prevention

PEDIATRIC GENESIS OF ATHEROSCLEROSIS Atherosclerosis results from a variety of pathophysiologic disturbances, some currently recognized, and many undoubtedly not yet recognized, which in aggregate are identified as risk factors. Genetic and environmental influences conjointly affect the incidence and the severity of these risk factors and, thus, coronary heart disease (CHD) risk. Prophylaxis should be designed to prevent or retard the development of arterial plaques. This suggests that diagnostic and preventive efforts should begin in childhood. Eating habits are also probably established in childhood, allowing their early modification. The atherosclerotic plaque appears to have its genesis in childhood. The data from wartime autopsies confirm the presence of mature atherosclerotic lesions by the end of the second decade and emphasize the importance of primary atherosclerosis prevention beginning in the first and second decades. While there are clearly genetic factors in CHD, variation in rates in differing geographic areas appears less likely to be related to genetic than to environmental differences. Marked differences in plasma cholesterol levels are found in children in different geographic areas, generally paralleling pediatric cholesterol and saturated fat intake and the incidence of adult coronary heart disease. The relationships of elevated total plasma cholesterol levels to the incidence of coronary heart disease are clearly established in adults.

Genesis of Statins

2009 ◽  
Author(s):  
Jie Jack Li
Keyword(s):  
Heart Disease ◽  
Thyroid Hormone ◽  
Large Scale ◽  
Hormone Treatment ◽  
Blood Cholesterol ◽  
Heart Attacks ◽  
Cholesterol Levels ◽  
The 1950S ◽  
Loss Of Libido ◽  
Artery Disease

As evidence grew that high blood cholesterol levels were linked to heart disease, scientists in both academia and industry began to look for drugs to lower cholesterol as early as the 1950s. Before Akira Endo discovered the first statin, mevastatin, in the 1970s, many things, including hormones, vitamins, and resins, were tried to lower cholesterol. Some worked, and some did not. Thyroid hormone was one of the fi st drugs used for that purpose. The cholesterol-lowering properties of dextro-thyroxine were discovered by serendipity. At one point, surgical removal of part of the thyroid gland had been used to relieve angina, the pain brought on by exercise in coronary artery disease. Doctors observed that thyroid removal also raised the blood cholesterol level, which in turn sped up arterial degeneration. By deduction, the doctors reasoned that taking thyroid hormone should then decrease blood cholesterol levels. Initial clinical trials proved this theory, and dextro-thyroxine was used to lower cholesterol beginning in the 1950s, when thyroid extract became a standard treatment for hypercholesterolemic (high cholesterol) patients. Unfortunately, too much thyroid hormone made patients tremble all the time. Later, a large-scale, long-term clinical trial named the “Coronary Drug Project” established the association of dextro-thyroxine with ischemic heart disease as a severe side eff ect in men. As a consequence, thyroid hormone treatment was discontinued. Women, in contrast to men, enjoy natural cardiac protection through the action of the female sex hormones, the estrogens. In 1930, a minute quantity of estrogen was isolated from the ovaries of 80,000 sows. In the 1950s, reports appeared that estrogen could lower blood cholesterol levels even more effectively than nicotinic acid, another anticholesterol drug used at the time. Unfortunately, men on estrogen for too long began to develop feminine traits, including breast enlargement and loss of libido, and other side effects, although they did acquire relative immunity from heart attacks until late in life. Due to the lack of safe and effiicacious drugs, some doctors seemed willing to take their chances with estrogens.

Trends in Plasma Cholesterol Levels in the Atherosclerosis Risk in Communities (ARIC) Study

2000 ◽  
Vol 30 (3) ◽  
pp. 252-259 ◽  
Author(s):  
Moyses Szklo ◽  
Lloyd E. Chambless ◽  
Aaron R. Folsom ◽  
Antonio Gotto ◽  
F. Javier Nieto ◽  
...  
Keyword(s):  
Plasma Cholesterol ◽  
Atherosclerosis Risk In Communities ◽  
Cholesterol Levels ◽  
Atherosclerosis Risk ◽  
Aric Study

Cholesterol at Birth and Age 1: Comparison of Normal and Hypercholesterolemic Neonates

PEDIATRICS ◽  
1974 ◽  
Vol 53 (4) ◽  
pp. 458-470
Author(s):  
Reginald C. Tsang ◽  
Ronald W. Fallat ◽  
Charles J. Glueck
Keyword(s):  
Cord Blood ◽  
Familial Hypercholesterolemia ◽  
Plasma Cholesterol ◽  
Blood Cholesterol ◽  
Live Births ◽  
Cholesterol Levels ◽  
Cholesterol Intake ◽  
Low Cholesterol ◽  
Minimal Estimate

Plasma cholesterol was evaluated at birth and at age 1 in 56 infants who had elevated cord blood cholesterol levels, and in 42 infants who had normal cord blood cholesterol levels. Both groups of infants came from a study of 1,800 unselected live births. Familial hypercholesterolemia was documented by three-generation transmission (from grandparent to parent to neonate) or by presence of tendinous xanthomatosis with hyper-beta-lipoproteinemia in eight neonates and kindreds. A minimal estimate of the heterozygote frequency of familial hyperlipidemia in unselected live births was 0.44% (8/1,800). On moderate-high cholesterol intake at age 1, three of four infants with familial hypercholesterolemia maintained distinctive elevations of plasma cholesterol. On low cholesterol diets, the distinction between four infants with familial hypercholesterolemia and normal or other hypercholesterolemic infants was blurred. Responsiveness to low cholesterol diet may hold promise in a long-term approach to normalization of plasma cholesterol in infants with familial hypercholesterolemia.

scholarly journals IndustrialTransFatty Acid and Serum Cholesterol: The Allowable Dietary Level

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Hiroyuki Takeuchi ◽  
Michihiro Sugano
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Serum Cholesterol ◽  
Unsaturated Fatty Acids ◽  
Plasma Cholesterol ◽  
Dietary Fats ◽  
Blood Cholesterol ◽  
Complex Situation ◽  
Dietary Level ◽  
Cholesterol Levels

Transfatty acid (TFA) from partially hydrogenated oil is regarded as the worst dietary fatty acid per gram due to its role in coronary heart disease. TFA consumption is decreasing worldwide, but some but not all observational studies indicate that TFA intake has little relevance to serum cholesterol levels in populations with low TFA intake (<1%E[percentage of total energy intake], <approximately 2 g/day). Few intervention trials examined the effect of TFAs on blood cholesterol at relatively low levels (<2%E); no definite evidence is available on the tolerable upper level of the intake. A series of our intervention studies in Japanese suggested that an industrial TFA intake at <1%Edoes not influence the serum cholesterol level. To establish allowable level, we must consider not only the dietary level of TFAs, but also the composition of dietary fats simultaneously consumed, that is, saturated and unsaturated fatty acids. These fatty acids strengthen or counteract the adverse effect of TFAs on serum cholesterol levels. In this review we describe the complex situation of the cardiovascular effects of industrial TFAs. The relationship between dietary industrial TFAs and concentration of plasma cholesterol should be evaluated from the viewpoint of dietary patterns rather than TFAs alone.　

scholarly journals Influence of simvastatin on bone regeneration of tibial defects and blood cholesterol level in rats

2006 ◽  
Vol 17 (4) ◽  
pp. 267-273 ◽  
Author(s):  
Ana Lia Anbinder ◽  
Juliana Campos Junqueira ◽  
Maria Nadir G. Mancini ◽  
Ivan Balducci ◽  
Rosilene Fernandes da Rocha ◽  
...  
Keyword(s):  
Cholesterol Level ◽  
Bone Repair ◽  
Plasma Cholesterol ◽  
Subcutaneous Administration ◽  
Blood Cholesterol ◽  
Blood Cholesterol Level ◽  
Water Group ◽  
Routes Of Administration ◽  
Cholesterol Levels ◽  
Significant Difference

The purpose of this study was to evaluate the effects of simvastatin, by oral or subcutaneous administration, on tibial defects regeneration and blood cholesterol level in rats. A surgical defect was made on the right tibia of 40 male animals assigned to 4 groups (n=10), based on two routes of administration and on the use or not of simvastatin: subcutaneous injection of simvastatin (7 mg/kg) (group AT) or only the vehicle of drug suspension (group AC), above the defect area, for 5 days; and 20 mg/kg of simvastatin macerated on water (group BT) or only water (group BC), orally, daily, during the whole observation period. The animals were sacrificed after 15 or 30 days, when blood samples were analyzed to check plasma cholesterol levels. Tibiae were removed and, after decalcification and routine laboratorial processing, histological and histomorphometrical analyses were carried out. ANOVA was used for statistical analysis at 5% signficance level. The histological and histomorphometrical analyses showed significant differences only between the experimental periods (p<0.05). Animals sacrificed after 30 days showed better bone repair (p<0.05). There was no statistically significant difference (p>0.05) for blood cholesterol levels between the groups. In conclusion, simvastatin administration either orally or subcutaneously did not improve bone repair of experimental tibial defects and did not alter blood cholesterol levels in rats.

scholarly journals Cholesterol lowering in pigs through enhanced bacterial bile salt hydrolase activity

1998 ◽  
Vol 79 (2) ◽  
pp. 185-194 ◽  
Author(s):  
I. De Smet ◽  
P. De Boever ◽  
W. Verstraete
Keyword(s):  
Bile Salt ◽  
Ldl Cholesterol ◽  
Lactobacillus Reuteri ◽  
Plasma Cholesterol ◽  
Hdl Cholesterol ◽  
Blood Cholesterol ◽  
Cholesterol Concentration ◽  
Control Group ◽  
Bile Salt Hydrolase ◽  
Cholesterol Levels

The effect of feeding liveLactobacillus reutericells containing active bile salt hydrolase (BSH) on plasma cholesterol levels was studied in pigs. During an experiment lasting 13 weeks, twenty pigs were fed on a high-fat, high-cholesterol, low-fibre diet for the first 10 weeks, and a regular pig diet for the last 3 weeks. One group of animals received, twice daily, 11·25 (SD 0·16) log10colony forming units of the potential probiotic bacteria for 4 weeks (from week 3 until week 7). From week 8 onwards, the treated group was again fed on the same diet as the control group without additions. The total faecalLactobacilluscounts were only significantly higher in the treated pigs during the first 2 weeks ofL. reuterifeeding. Based on limited data, it was suggested that the administeredLactobacillusspecies had caused a temporary shift within the indigenousLactobacilluspopulation rather than permanently colonizing the intestinal tract. The probiotic feeding brought about significant lowering (P≤ 0·05) of total and LDL-cholesterol concentrations in the treated pigs compared with the control pigs, while no change in HDL-cholesterol concentration was observed. The data for faecal output of neutral sterols and bile salts were highly variable between the animals of each group, yet they indicated an increased output in the treated pigs. Although the blood cholesterol levels went up in both groups during the 3 weeks following theLactobacillusadministration period, significantly lower serum total and LDL-cholesterol levels were observed in the treated pigs. During the final 3 weeks of normalization to the regular diet, cholesterol concentrations significantly decreased in both animal groups and the differences in total and LDL-cholesterol concentrations between the groups largely disappeared.

scholarly journals Management of Hypercholesterolemia Through Dietary ß-glucans–Insights From a Zebrafish Model

2022 ◽  
Vol 8 ◽  
Author(s):  
Adnan Hussain Gora ◽  
Saima Rehman ◽  
Viswanath Kiron ◽  
Jorge Dias ◽  
Jorge M. O. Fernandes ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Cholesterol ◽  
Cholesterol Biosynthesis ◽  
Dietary Cholesterol ◽  
Blood Cholesterol ◽  
Control Group ◽  
Zebrafish Model ◽  
Cholesterol Lowering ◽  
Cholesterol Levels ◽  
Transcriptomic Changes

Consumption of lipid-rich foods can increase the blood cholesterol content. β-glucans have hypocholesterolemic effect. However, subtle changes in their molecular branching can influence bioactivity. Therefore, a comparative investigation of the cholesterol-lowering potential of two β-glucans with different branching patterns and a cholesterol-lowering drug, namely simvastatin was undertaken employing the zebrafish (Danio rerio) model of diet-induced hypercholesterolemia. Fish were allocated to 5 dietary treatments; a control group, a high cholesterol group, two β-glucan groups, and a simvastatin group. We investigated plasma total cholesterol, LDL and HDL cholesterol levels, histological changes in the tissues, and explored intestinal transcriptomic changes induced by the experimental diets. Dietary cholesterol likely caused the suppression of endogenous cholesterol biosynthesis, induced dysfunction of endoplasmic reticulum and mitochondria, and altered the histomorphology of the intestine. The two β-glucans and simvastatin significantly abated the rise in plasma cholesterol levels and restored the expression of specific genes to alleviate the endoplasmic reticulum-related effects induced by the dietary cholesterol. Furthermore, the distinct patterns of transcriptomic changes in the intestine elicited by the oat and microalga β-glucans impacted processes such as fatty acid metabolism, protein catabolic processes, and nuclear division. Oat and microalgal β-glucans also altered the pattern of lipid deposition in the liver. Our study provides insights into the effectiveness of different β-glucans to alleviate dysfunctions in lipid metabolism caused by dietary cholesterol.

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