First hand smoke causes mutation in cardiovascular cells

First hand smoke causes mutation in cardiovascular cells, alters DNA inside cells

Smoking leads to a significant decrease in the levels of a fatty acid called arachidonic acid in the body’s blood vessels. The enzyme that stores arachidonic acid in cells, called hydroxylases, is suppressed by the high levels of a metabolite of nicotine called NNAL. New findings published in the journal Molecular Psychiatry show that the suppression of arachidonic acid levels in endothelial cells by NNAL not only impairs cholesterol metabolism, but also affects DNA inside cells.

Arachidonic acid is a type of lipid (fat) that is important for normal cell function. Arachidonic acid is the basis of the skin, hair, nails, and the lubricating secretions of the mouth and digestive tract. It is also a component of the brain and other areas of the central nervous system.

What nicotine is to the brain, tar is to the lungs.

Tobacco smoke contains significant amounts of complex and dangerous toxins that damage lung tissue and are associated with disease and death.

In 2010 the World Health Organization described smoking as “the leading preventable cause of death worldwide.”According to the U.S. Department of Health and Human Services, “about 17% of all deaths in the United States each year are due to smoking (whether or not the user is a current smoker)”.Non-smokers, on the other hand, are exposed to a significant number of carcinogens every day.According to research from the London School of Hygiene and Tropical Medicine, one cigarette smoker will inhale more than 1,000 chemicals, and smokers will expose their smokers are exposed to several hundred.According to Health Canada, smokers who light up each day expose themselves to ten times more carcinogens than smokers who never smoke.

Tobacco smoke also contains dozens of toxins including:

In addition, cigarette smoke contains nicotine, a highly addictive and highly toxic substance.

When smokers take in nicotine, they are also exposed to chemicals that can damage their brain function and increase the risk of tobacco-related diseases,Smoking cigarettes increases the risk of lung cancer.While lung cancer causes only 2–3% of all deaths in North America, it causes 40% of all lung cancer deaths in the world.Smoking causes nearly 60% of all lung cancer deaths in Canada and almost 70% in the United States.

Other lung cancers (which are not caused by smoking) account for 8–14% of lung cancer deaths.It is recommended that people who are at risk for lung cancer should quit smoking completely or reduce the amount of tobacco in their diet.Statistics show that tobacco use is a very strong risk factor for developing non-small cell lung cancer.It is estimated that nearly half of all non-small cell lung cancers diagnosed each year are attributable to smoking.Smoking is also a strong risk factor for developing squamous cell lung cancer (SCLC).t is estimated that approximately 10% of all SCLC cases are caused by smoking.Women who smoke have a 15-times increased risk of developing SCLC than non-smokers.

And women who smoke have a 50-fold increased risk of developing SCLC than women who have never smoked.Squamous cell carcinoma is a rare but aggressive type of lung cancer that develops in the squamous cells of the respiratory tract, particularly in the linings of the respiratory bronchi and trachea.SCLC accounts for approximately 4% of all cases of lung cancer and 15% of all cases of non-small cell lung cancer.SCLC is the most common type of non-small cell lung cancer in women.Although the increased risk for developing SCLC is lower than the risk for developing non-small cell lung cancer, the cause is similar.

It is estimated that smoking was the cause of 5% to 7% of cancers in Canada and the U.S. in 1992.In 1991, the most recent year for which full data was available, 4.7% of cancers and 2.4% of all deaths worldwide were attributable to smoking.According to a 2004 report by the World Health Organization, smoking was the single greatest risk factor for cancer.

Not only does smoking cause lung cancer, but second hand smoke is also thought to increase the risk of lung cancer in people who do not smoke.In 2008 the WHO stated that people who did not smoke were at a lower risk for lung cancer than those who did.

The following information comes from the National Cancer Institute and is about smoking and lung cancer prevention:

Smoking is the single greatest risk factor for developing lung cancer.Smoking causes approximately 80% of all cases of lung cancer, and is estimated to cause about 70% of all lung cancer deaths.The number of lung cancer deaths attributable to smoking is estimated to be as high as 443,000 and to exceed 715,000 in the U.S.

The estimated prevalence of cigarette smoking in adults around the world is about 20%.Most people who smoke began by the age of 18, and about 35% of high school and college students smoke.Smoking is the most common cause of cancer deaths in the developed world, and has now overtaken high blood pressure as the number one cause of premature death.

Health experts worldwide are concerned about the impact of smoking on public health, with a worldwide public health cost estimated to be about $4 trillion per year.According to a 2007 report by the World Health Organization, tobacco use causes one in every five deaths worldwide and costs more than $1 trillion each year in direct health care expenses alone.Over 14 million smokers die prematurely each year, and over 3.3 billion people use tobacco products.

Tobacco’s global health burden is equivalent to that of second-hand smoke, traffic accidents and all alcohol-related deaths combined.The report adds that tobacco already kills some 8 million people each year.One of the main methods of preventing smoking is stopping young people from taking up smoking.Some organizations campaign against smoking in the workplace and in restaurants.A law in California against smoking in indoor workplaces, public places and cars went into effect on 1 May 2007.There has also been opposition to smoking in homes.

Several such laws have been passed across the country, although some have been challenged by lawyers, some states have upheld them, and others have been struck down by courts.In the United States, some states have also approved legislation banning smoking in public places, including restaurants, cafes, bars, arenas, hotels and other public places.When smokers are given a drug to counteract the effects of smoking, these toxins are more likely to enter the brain, causing brain damage.The liver produces arachidonic acid and converts it into the toxic molecule, NNAL, which amages DNA.

Researchers at Johannes Gutenberg University Mainz (JGU) and University Hospital Frankfurt (Oder), led by Prof. Dr. Edzard Ernst, have been investigating the molecular mechanisms behind this connection.”The cardiovascular effects of smoking for several years. We are now able to understand the molecular basis for how the suppression of the production of arachidonic acid by NNAL affects cells’ DNA,” says Ernst, Professor of Oncology at the University of Exeter Medical School.

During normal functioning, hydroxylases are activated by arachidonic acid to make several other fatty acids that can then be recycled for metabolic use, such as arachidonic and docosahexaenoic acids (DHA and EPA), essential for brain function. NNAL blocks the production of these other fatty acids by depleting the pool of available arachidonic acid and so interfering with lipid metabolism.

“Because we wanted to examine the effect of NNAL on both cholesterol metabolism and the expression of genes involved in brain development and behavior, we first needed to suppress the production of arachidonic acid in blood vessels by the enzyme that stores arachidonic acid in cells,” says Dr. Daniela Pfalzgraf, who is a visiting fellow at the Institute of Cancer Research in London.

The researcher now showed that the gene EZH2, which is responsible for the synthesis of arachidonic acid, is inhibited by the high levels of NNAL in blood vessels. This renders the enzyme unable to make arachidonic acid. “Excessive arachidonic acid affects the metabolism of cholesterol,” explains Pfalzgraf.

Arachidonic acid is then transported away from the cells to other locations in the body. Because arachidonic acid is not immediately available, the liver begins to make NNAL. “This causes both cholesterol and arachidonic acid to be stored away from the cell’s core, resulting in a drastic decrease in the levels of both,” explains Pfalzgraf.

During this time period, the enzyme EZH2 is suppressed. However, EZH2 levels will eventually rise again, leading to the production of arachidonic acid and the return of EZH2 to normal levels. NNAL also inhibits the expression of EZH2.

“These results show that the reduction in cholesterol and the storage of arachidonic acid are linked with an impairment in the brain’s ability to function properly. Smoking is therefore a significant risk factor for cardiovascular disease,” Pfalzgraf says.

“The most interesting aspect of our results,” adds Prof. Ernst, “is that they are based on biochemical studies in which we were able to see how NNAL specifically affects gene expression.”

The research group, led by Prof. Ernst, in collaboration with the research group of Dr. Dominik Kraus from the Chair of Pharmacoepidemiology, discovered that the NNAL gene is localized to the nucleus and is not expressed in any of the brain’s primary regions.

Furthermore, they showed that EZH2 production is influenced by the levels of arachidonic acid. In addition, genetic analysis of brain samples of smokers revealed that this level of arachidonic acid is directly linked with EZH2 expression.

A limitation of the current study is that the data from the drug combinations did not allow for a detailed comparison with the effects of smoking without NNAL suppression, Pfalzgraf says. “However, we believe that these experiments have only begun,” she says.

In addition, the current study and the research group’s previous studies on the molecular mechanisms of smoking-associated disease have largely depended on blood samples. This approach is time-consuming and results in a limited number of participants. The “intrinsic” behavior of neurons, which are classified as stem cells, differs from that of blood stem cells and is therefore difficult to investigate, Pfalzgraf explains.

However, the data from the current study may pave the way for new methods of studying and monitoring NNAL.

The researchers now plan to carry out clinical studies of the effects of NNAL on blood vessels, and how NNAL affects the metabolism of different compounds, in collaboration with researchers from several different countries. “Our new data show that the biochemical markers we identified could be used to evaluate possible mechanisms of NNAL-induced damage in blood vessels,” says Prof. Ernst.

The researchers are currently planning to conduct clinical trials to study NNAL’s effect on the liver and heart.

“Neuroscientists are interested in the effect of NNAL on the individual gene expression in the brain,” Pfalzgraf says. “This could shed new light on the causes of psychiatric and neurodegenerative diseases.”