Advanced Cell Technology (ACT; Worcester, Massachusetts) reports that nuclear transfer cloning can be used to repair and regenerate the damage done to an infarcted heart. The results of a study, appearing online in the American Heart Association's (Dallas, Texas) journal, Circulation, by ACT and its collaborators, provide the first experimental evidence in animals of the successful use of cloning techniques to repair a severely damaged organ. One aspect of the debate over the use of therapeutic cloning has centered on the question of whether cloned cells would be healthy enough to be of practical use in cell therapy.

Using a mouse model, ACT and collaborators isolated and injected cloned stem cells into the region of the heart adjacent to the damaged heart tissue. The cloned stem cells replaced nearly 40% of the scar tissue at the site of injury and improved the ability of the heart to beat normally. "This study introduces an important new paradigm," said Robert Lanza, vice president of medical and scientific development at ACT and lead author of the study. "Cloned cells are not only histocompatible, but [also] are more youthful and potentially of greater therapeutic value than adult stem cells."

The regenerated heart tissue was composed not only of heart muscle cells but also of blood vessels that connected with the coronary circulation. The cloned myocytes were functionally competent, expressed contractile proteins and were electrically and mechanically coupled to other heart cells. The newly formed coronary arterioles and capillary structures contained blood and likely contributed to tissue oxygenation. Cardiac replacement resulted in an improvement of ventricular hemodynamics and a reduction of diastolic wall stress.

A relatively small number of cells were injected in the region bordering the infarct, suggesting that the magnitude of myocardial regeneration obtained with stem cells from cloned embryos was superior to that previously achieved with adult bone marrow cells. Complete healing of the infarcted region in the mouse occurred in three weeks, strengthening the relevance of the present study to ischemic heart disease and post-infarction heart failure in humans.

Michael West, chief executive officer of ACT, said, "Medical researchers are beginning to imagine a day when science can conquer this dreaded disease, unlocking the power of stem cells to mend broken hearts. The ability of therapeutic cloning to theoretically make any cell or tissue type in the human body, and cells that would likely be accepted by the body as 'self' underscores the importance of our nation leading the world in the science of regenerative medicine."

The ACT researchers collaborated with scientists from the Cardiovascular Research Institute at New York Medical College, Memorial Sloan-Kettering Cancer Center (both New York) and the RIKEN Center of Developmental Biology (Kobe, Japan).

Premature heart disease gene locus found

Scientists at The Cleveland Clinic (Cleveland, Ohio) say they have identified a gene locus that may begin to explain why some people are more susceptible to premature coronary artery disease and heart attack than others, with the research results published in the February issue of the American Journal of Human Genetics. "This discovery brings us even closer to identifying an underlying gene responsible for the most aggressive form of coronary heart disease," said Eric Topol, MD, chairman of the department of cardiovascular medicine at The Cleveland Clinic.

The gene locus was discovered by examining the genetic makeup of 428 families with premature heart attack or coronary artery disease (CAD). Every family had at least two siblings with premature CAD. To control for other risk factors, individuals with high cholesterol and insulin-dependent diabetes were excluded from the study, and the study also was limited to 45-year-old men and younger and 50-year-old women and younger, at the time they experienced heart attacks, to increase the likelihood that genetics was a contributing factor. Overall, 1,613 individuals participated in the research, 91.7% of them Caucasian.

After participants were identified, a genome-wide scan was conducted to search for areas specifically linked to heart attack and CAD. The gene locus, or "linkage peak," was found on chromosome 1p34-36. The LOD (logarithm of the odds score) of 11.7 indicates the chance that this locus would appear in the general population without premature heart disease is less than one in 10 million. It is by far the most significant linkage peak for heart attack yet identified, with four prior studies reported from populations in India, Finland, Australia and Germany, Topol said.

Atherosclerosis strikes early in lupus

A clinical study reported in the Dec. 18 issue of the New England Journal of Medicine indicated that atherosclerosis occurs earlier in lupus patients and, contrary to what was previously thought, is independent of many risk factors normally associated with cardiovascular disease. Jane Salmon, MD, director of the Mary Kirkland Center for Lupus Research at the Hospital for Special Surgery and professor of medicine at Weill Cornell Medical College (both New York), and Mary Roman, MD, a cardiologist and professor of medicine at Weill Cornell and attending physician at New York-Presbyterian Hospital/Weill Cornell Medical Center, were co-principal investigators of this first-of-its-kind clinical study.

According to Salmon, "Surprisingly some of the young women with lupus whom we care for at Hospital for Special Surgery were presenting with heart attacks. We hypothesized that this unexpected finding was due to chronic immune system activation leading to damage of coronary blood vessels." The study tested this possibility by assessing the prevalence of atherosclerosis and cardiovascular disease risk factors in a population of lupus patients compared to that of matched healthy individuals, about 200 in each group. "While lupus is best known for leading to kidney, neurologic, skin and brain disease, we now know that lupus is also directly responsible for atherosclerotic plaque build-up that may result in heart attack, stroke, and other negative cardiovascular outcomes," Roman said.

The researchers added, "Further clinical studies are needed to determine the best biomarker for the propensity to develop plaque, as well as the best treatment whether it is immunosuppressant drugs, statins, or other types of medications. However, the negative correlation between atherosclerosis and immunosuppressive treatments suggests that more vigorous therapy might decrease the likelihood and burden of atherosclerosis in lupus and, perhaps, in other chronic inflammatory diseases as well."

Of the enrolled patients with lupus, 37.1% were found to have atherosclerosis, compared to 15.2% of lupus-free patients with matched cardiovascular disease risk factors and demographic variables, indicating that lupus increased the likelihood of having atherosclerosis by 140%. The difference was even more pronounced in lupus patients 40 years and younger for whom the risk was increased by 480%. Not only is atherosclerosis more prevalent in patients with lupus, but the study also provides evidence that lupus disease-related factors cause atherosclerosis.

This contradicts the prevailing hypothesis that atherosclerosis in lupus patients is attributable to an increased frequency of conventional risk factors such as hypertension, high cholesterol, smoking, and diabetes. As evidence, the authors note that while immunosuppressive (anti-inflammatory) drugs have the potential to exacerbate these risk factors, in fact, lupus patients who received the treatments showed a lower prevalence of atherosclerosis.

The study is supported by grants from the National Institute of Arthritis, Musculoskeletal and Skin Disease; the National Heart, Lung and Blood Institute; the U.S. Public Health Service; the Mary Kirkland Center for Lupus Research and the Bugher Foundation.

Magnesium a heart-healthy material

New research shows that the trace element magnesium has an important role to play in saving the lives of coronary artery bypass surgery patients and that intake of dietary magnesium is associated with a reduced risk of coronary heart disease. Patients with good magnesium levels, who have undergone surgery to replace damaged sections of their coronary arteries, are less likely to die, or have a heart attack, in the following year than those with poor magnesium status.

U.S. researchers, in a project spanning 30 years, also have also shown that intake of this trace element in the diet also appears to cut the risk of coronary heart disease. Their findings, which indicate a strong link between good magnesium status and low levels of coronary heart disease, were reported in the American Journal of Cardiology.

The researchers at Duke University Medical Center (Durham, North Carolina) reported that patients with low magnesium levels had a twofold increased incidence of heart attack and all-cause mortality rate as long as one year after surgery, compared to those with normal magnesium levels. A total of 957 patients having cardiac bypass surgery for the first time took part.

In another 30-year study, men aged 45 to 68 were recruited as part of the Honolulu Heart Program and their dietary intake of magnesium was assessed. Researchers at the University of Virginia School of Medicine (Charlottesville, Virginia), who followed the progress of the men, identified 1,431 incident cases of coronary heart disease (CHD).

Differences in risk of CHD were clearly apparent within 15 years. Those with the lowest magnesium intake (the lowest fifth) were twice as likely to have had a CHD problem as those with the highest intake (the highest fifth.)