Lcat As A Therapeutic Target For Dyslipidemia
Overexpression of human LCAT in rabbits and co-overexpression with CETP in mice has shown protection against diet-induced atherogenesis . Conversely, several mutations in apoAI that impair its LCAT activation are strongly correlated with reduced HDL levels . Physiologically, LCAT binds FC and phosphatidylcholine , transferring the acyl chain at the sn-2 position of PC to FC, producing CE and lyso-PC. LCAT, an interfacial enzyme , functions on the surface of HDL particles. Binding to the HDL surface activates the enzyme, but optimal activity is reached only after association with a cofactor. The most potent activator of LCAT is apoAI, and the mechanism of activation is thought to be similar to that of PL by colipase which forms a 1:1 complex with PL . A three-dimensional structure for LCAT is currently unavailable, although a computational model has been proposed . The model suggests that LCAT has an architecture similar to that of the family of / hydrolases . Consistent with this hypothesis, mutational experiments that changed the catalytic residues Ser181 , His377, and Asp345 into Ala resulted in complete loss of, or severe reductions in, enzyme activity.
What You Can Control:
- Unhealthy diet: Too much saturated fat and trans fat in your diet can increase your LDL cholesterol levels. Most saturated fat comes from animal products such as meats , butter, cream, cheese and other whole milk dairy products. Trans fat is found in processed foods which include stick margarine, crackers, and baked goods.
- Smoking: Smoking is known to lower HDL cholesterol and increase the risk of heart disease.
- Lack of exercise: Low physical activity leads to low HDL cholesterol.
- Excess weight: Being overweight can lead to higher LDL cholesterol levels and lower HDL cholesterol levels, in addition to higher triglycerides . Losing weight can help improve your cholesterol levels.
Hdl Versus Ldl Cholesterol
There are two main types of cholesterol: high-density lipoprotein and low-density lipoprotein . Lipoproteins are made of fat and proteins. Cholesterol moves through your body while inside lipoproteins.
HDL is known as good cholesterol because it transports cholesterol to your liver to be expelled from your body. HDL helps rid your body of excess cholesterol so its less likely to end up in your arteries.
LDL is called bad cholesterol because it takes cholesterol to your arteries, where it may collect in artery walls. Too much cholesterol in your arteries may lead to a buildup of plaque known as atherosclerosis. This can increase the risk of blood clots in your arteries. If a blood clot breaks away and blocks an artery in your heart or brain, you may have a stroke or heart attack.
Plaque buildup may also reduce blood flow and oxygen to major organs. Oxygen deprivation to your organs or arteries may lead to kidney disease or peripheral arterial disease, in addition to a heart attack or stroke.
Centers for Disease Control , over 31 percent of Americans have high LDL cholesterol. You may not even know it because high cholesterol doesnt cause noticeable symptoms.
The only way to find out if your cholesterol is high is through a blood test that measures cholesterol in milligrams per deciliter of blood . When you get your cholesterol numbers checked, youll receive results for:
To treat high cholesterol, doctors often recommend these lifestyle changes:
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Role In The Innate Immune System
LDL interfere with the quorum sensing system that upregulates genes required for invasive Staphylococcus aureus infection. The mechanism of antagonism entails binding apolipoprotein B to a S. aureusautoinducer pheromone, preventing signaling through its receptor. Mice deficient in apolipoprotein B are more susceptible to invasive bacterial infection.
Why Is Ldl Cholesterol Called Bad Cholesterol
ByAdrian Whittle | Submitted On July 22, 2007
High cholesterol is a leading cause of thickening of the arteries. This is known as atherosclerosis and can lead to other cardiovascular diseases, including heart disease. If someone has high cholesterol they are advised to change their diet and take more exercise. This article will explain what cholesterol does to the body, in particular, reference to LDL cholesterol and why it is considered bad for the body.
Cholesterol is produced naturally in the liver. It provides a number of vital functions within the body but gets most attention when there is too much of it in our bodies and thus causes problems. Too much cholesterol is often due to eating too many products that are high in cholesterol, notably animal products like meat and dairy produce. Cholesterol is absorbed by the digestive system from these types of foods.
Cholesterol, like other byproducts of digested food, such as triglycerides, are transported throughout the body via the bloodstream. However, cholestrol is not soluble in blood so it is attached to lipoproteins that act as a transport for cholesterol.
Lipoproteins can be classified into 5 types with regards to cholesterol transport. The one that we are concerned with in this article is known as low density lipoprotein . It’s job is to bind with cholesterol and take it to all parts of the body to do it’s vital work. This combination of LDL and cholesterol gets the name LDL Cholesterol.
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How To Increase Hdl Cholesterol
Although HDL levels are driven by family genetics, you can improve HDL levels in three key ways:
- If you are a smoker, research clearly shows that quitting smoking can increase HDL.
- Adopting a heart-healthy diet low in fat and high in fiber can also modestly raise your HDL.
- Aerobic exercise can also have positive effects on HDL. Have trouble exercising? Find a buddy research shows it helps motivate you. That exercise can be as simple as increasing the amount of walking you do each week.
Lastly, although primarily used to decrease high LDL, some statin medications may potentially increase HDL levels moderately. Any medical treatment option should be discussed with your doctor. Importantly, high HDL does not protect you from the untoward effects of high LDL.
Why Do We Need Cholesterol
There is cholesterol in every cell in your body. It plays vital roles in how your body works, and it’s especially important in your brain, nerves and skin.
Cholesterol has three main jobs:
- Its part of the outer layer, or membrane, of all your cells.
- Its used to make vitamin D and steroid hormones which keep your bones, teeth and muscles healthy.
- Its used to make bile, which helps to digest the fats you eat.
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What Is Ldl Cholesterol
Cholesterol is carried through the blood on two types of proteins called lipoproteins. These lipoproteins include LDL , which is sometimes referred to as bad cholesterol, and HDL , or what is typically referred to as good cholesterol.
The science over good and bad cholesterol has shifted quite a bit recently, so how can you be sure that youre not putting your health in danger? Read on for everything you need to know about LDL backed by the most recent science.
Why Would My Cholesterol Go Up Suddenly
your cholesterolhighcholesterolincrease your cholesterol
In this manner, what are the symptoms of high cholesterol in the body?
Ask about being tested for high cholesterol. You develop symptoms of heart disease, stroke, or atherosclerosis in other blood vessels, such as left-sided chest pain, pressure, or fullness dizziness unsteady gait slurred speech or pain in the lower legs.
Beside above, how quickly does cholesterol levels change? For most people, levels drop dramatically within three weeks. Whats heartening to know is that many people do not need to rely on prescription drugs and their possible side effects to reduce their cholesterol.
Similarly, it is asked, what can cause high cholesterol besides diet?
These are six factors besides food that can increase your risk of high cholesterol.
- Obesity. When you hear the word obese, you probably think of an extremely large person.
- Lack of exercise.
Why is my LDL suddenly high?
Health Problems That Raise Cholesterol Levels. While genes or an unhealthy diet are often the causes of high cholesterol, many health conditions can also be culprits. Many people have high cholesterol because of physical inactivity or a diet too high in saturated fats, or because it runs in the family.
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What Makes Ldl Cholesterol Too High
A range of medical and lifestyle factors cause high LDL, including:
- Diet: Diets high in saturated fats, salts, and cholesterol and low in healthy proteins and fiber can lead to high LDL.
- Lack of physical activity: Not getting enough exercise and being sedentary can also push levels up. You may see higher LDL if you don’t get a minimum of 30 minutes a day of activity.
- Weight status: For some, being overweight or extremely overweight greatly increases the chances of developing high LDL.
- Alcohol and tobacco: Smoking and drinking are both associated with high cholesterol, among many other detrimental effects on health.
- Genetics: High LDL can be inherited, a condition called familial hypercholesterolemia . The severity of FH ranges, but those with the homozygous formin which both parents are carriers of the faulty genemay have extremely high amounts of this type of cholesterol.
- Medications: Taking several classes of drugs can lead to spikes in LDL. These include those for heart disease, high blood pressure, inflammation, certain viruses, and seizures, among other conditions. Talk to a doctor about how these prescriptions may impact cholesterol.
- Health conditions: Diseases and conditions that cause high LDL include type 2 diabetes, pregnancy, chronic kidney disease, and hypothyroidism.
Other Risks And Follow
Your cholesterol numbers don’t determine your destiny. Remember, other things besides cholesterol can also lead to heart disease. Diabetes, smoking, high blood pressure, obesity, exercise, and genetics are important as well.
People with normal cholesterol can have heart disease people with high cholesterol can have healthy hearts. Overall, though, more people whose cholesterol levels are off will get heart disease.
Experts recommend follow-up cholesterol testing every 5 years for most people. If your lipid results aren’t what you and your doctor had hoped for, or if you have other reasons to be concerned about heart disease, you’ll need cholesterol tests more often.
American Heart Association: “How to Get Your Cholesterol Tested,” “Triglycerides,” “Triglycerides: Frequently Asked Questions,” “About Metabolic Syndrome,” âWhat Are High Blood Cholesterol and Triglycerides?â “LDL and HDL Cholesterol: Whatâs Bad and Whatâs Good?”
Kontush, A. Arteriosclerosis, Thrombosis, and Vascular Biology, 2003.
Tabas, I. Journal of Clinical Investigation, 2002.
National Heart, Lung, and Blood Institute: “High Blood Cholesterol: What You Need to Know.”
Jenkins, D. JAMA, 2003.
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How Can I Lower My Cholesterol
There are two main ways to lower your cholesterol:
- Heart-healthy lifestyle changes, which include:
- Heart-healthy eating. A heart-healthy eating plan limits the amount of saturated and trans fats that you eat. Examples include the Therapeutic Lifestyle Changes diet and the DASH Eating Plan.
- Weight Management. If you are overweight, losing weight can help lower your LDL cholesterol.
- Physical Activity. Everyone should get regular physical activity .
- Managing stress. Research has shown that chronic stress can sometimes raise your LDL cholesterol and lower your HDL cholesterol.
- Quitting smoking.Quitting smoking can raise your HDL cholesterol. Since HDL helps to remove LDL cholesterol from your arteries, having more HDL can help to lower your LDL cholesterol.
- Drug Treatment. If lifestyle changes alone do not lower your cholesterol enough, you may also need to take medicines. There are several types of cholesterol medicines available, including statins. The medicines work in different ways and can have different side effects. Talk to your health care provider about which one is right for you. While you are taking medicines to lower your cholesterol, you should continue with the lifestyle changes.
NIH: National Heart, Lung, and Blood Institute
What Is A Good Ldl To Hdl Ratio
In general, the higher your HDL, and the lower LDL, the better off you are. Optimal cholesterol levels are determined by looking at the ratio of HDL cholesterol to total cholesterol. This is calculated by dividing total cholesterol score by your HDL result, so if your total score is 150, and your HDL is at 50, youd score a 3:1.
Generally speaking, the higher this number, the higher the risk of heart problems. Doctors want to see a ratio below 5:1, with those below 3.5:1 considered ideal. Since lowering LDL causes total cholesterol numbers to drop, it promotes a better cholesterol ratio.
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What Are Recommended Cholesterol Levels By Age
Lipids are the by-products of common fat we eat. Lipids are classified as triglycerides , diglycerides , and steroids. Cholesterol is a steroid helping in the formation of cell membranes and hormones. Further, this cholesterol is classified as Low-Density Lipoprotein or LDL, and High-Density Lipoprotein or HDL also called good cholesterol. VLDL is another type of cholesterol secreted by the liver into your bloodstream. VLDL stands for Very-Low Density Lipoprotein. Lipoproteins are formed partly by proteins and partly fat. All three types of lipoproteins vary in the proportion that is made of cholesterol, protein, and triglycerides. VLDL has more of triglycerides, LDL more of cholesterol, and HDL more of protein. That is the reason, LDL and VLDL are together known as the bad cholesterol, they both have a significant role in the formation of plaque. Now, plaque is a thick solid sticky mass made of fat, cholesterol, calcium, and other similar substances that get deposited in the arterial lumen interrupting the blood flow.
All in all, both types of bad cholesterol adversely affects your heart health either by getting deposited in the lumen of your arteries or under your skin and in the liver. If the lumen is completely choked, the organ may not get any blood supply. The plaque may burst and move to smaller arteries blocking them completely.
According to the American Heart Association, the following are the age-wise recommended cholesterol levels:
Estimation Of Ldl Particles Via Cholesterol Content
Chemical measures of lipid concentration have long been the most-used clinical measurement, not because they have the best correlation with individual outcome, but because these lab methods are less expensive and more widely available.
The lipid profile does not measure LDL particles. It only estimates them using the Friedewald equationby subtracting the amount of cholesterol associated with other particles, such as HDL and VLDL, assuming a prolonged fasting state, etc.:
- L T
- where H is HDL cholesterol, L is LDL cholesterol, C is total cholesterol, T are triglycerides, and k is 0.20 if the quantities are measured in mg/dl and 0.45 if in mmol/l.
There are limitations to this method, most notably that samples must be obtained after a 12 to 14 h fast and that LDL-C cannot be calculated if plasma triglyceride is > 4.52 mmol/L . Even at triglyceride levels 2.5 to 4.5 mmol/L, this formula is considered inaccurate. If both total cholesterol and triglyceride levels are elevated then a modified formula, with quantities in mg/dl, may be used
- L T
This formula provides an approximation with fair accuracy for most people, assuming the blood was drawn after fasting for about 14 hours or longer, but does not reveal the actual LDL particle concentration because the percentage of fat molecules within the LDL particles which are cholesterol varies, as much as 8:1 variation.
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Plant Sterols Can Lower Cholesterol Levels
Plant sterols are found naturally in plant foods including sunflower and canola seeds, vegetable oils and in nuts, legumes, cereals, fruit and vegetables. Some margarine and milks have concentrated plant sterols added to them. Margarines enriched with plant sterolslower LDL cholesterol in most people if the correct amount is eaten .
Are Test Results Accurate
While no test is always accurate, measurements of blood cholesterol are an effective tool for estimating your risk of cardiovascular disease. Various factors can affect the accuracy of a cholesterol test:
- Direct vs calculated testing: While calculated LDL cholesterol levels are sufficient in most cases, direct testing provides more accurate results in patients with elevated triglyceride levels. Patients who may have elevated triglyceride levels include those diagnosed with type II diabetes or obesity, patients with a history of considerable alcohol intake, and patients taking medication to increase triglycerides.
- Fasting: In most cases, a lipid profile requires fasting. Eating within 8-12 hours before a lipid panel may increase the level of triglycerides in your bloodstream. Because this increased level of triglycerides could affect the accuracy of calculated LDL cholesterol values, your doctor may request that you refrain from eating prior to your blood draw.
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Checking Your Blood Cholesterol Level
A cholesterol screening is an overall look at the fats in your blood. Screenings help identify your risk for heart disease. It is important to have what is called a full lipid profile to show the actual levels of each type of fat in your blood: LDL, HDL, triglycerides, and others. Talk with your healthcare provider about when to have this test.
Why Is Ldl Considered A Bad Cholesterol Type
“Bad” Cholesterol LDL has historically been termed “bad” because it has the ability to collect as plaque in your arteries and eventually obstruct them. However, this term should be used with caution, since not all forms of LDL are equal. In fact, there are three different types of LDL: good, bad, and more bad.
Good LDL helps transport oxygen around your body and removes toxins. It also plays a role in immune function by helping fight off infections. Bad LDL collects in areas of the heart called coronary arteries so they can carry oxygenated blood to other parts of the heart. Too much bad LDL can lead to heart disease.
More bad LDL is found in people who have high levels of triglycerides. Triglycerides are a form of fat that gets stored in cells instead of being released into the bloodstream. When you have high levels of triglycerides, your liver produces more bad LDL in order to remove excess triglycerides from your body. High levels of bad LDL can increase your risk of having a heart attack or stroke.
Finally, very low density lipoprotein is another name for triglyceride-rich lipoproteins. As its name suggests, VLDLs are very dense – about 1,000 times heavier than water.
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