Hemoglobin (Hb) uniquely associates with proinflammatory HDL in atherogenic mice and coronary heart disease (CHD) patients. In this paper, we report that Hb and its scavenger proteins, haptoglobin (Hp) and hemopexin (Hx) are significantly increased in apoA-1-containing particles of HDL both in mouse models of hyperlipidemia and in CHD patients, when compared with wild type mice and healthy donors, respectively. We further demonstrate that the association of Hb, Hp, and Hx proteins with HDL positively correlates with inflammatory properties of HDL and systemic inflammation in CHD patients. Interestingly, HDL from Hp(-/-) mice under atherogenic conditions does not accumulate Hb and is anti-inflammatory, suggesting that (i) Hp is required for the association of Hb with HDL and (ii) Hb.Hp complexes regulate the inflammatory properties of HDL. Moreover, treatment of apoE(-/-) mice with an apoA-1 mimetic peptide resulted in significant dissociation of Hb.Hp complexes from HDL and improvement of HDL inflammatory properties. Our data strongly suggest that HDL can become proinflammatory via the Hb.Hp pathway in mice and humans, and dissociation of Hb.Hp.Hx complexes from apoA-1-containing particles of HDL may be a novel target for the treatment of CHD.
Atherosclerosis Research Unit, Department of Medicine/Cardiology
Wednesday
Monday
Experts Recommend Using Haemoglobin A1C Levels for Making a Diabetes Diagnosis
HEMOGLOBIN A1C
By Bruce Sylvester
NEW ORLEANS -- June 6, 2009 -- A patient who reaches a glycosylated hemoglobin (Hb A1C) level of 6.5% should be diagnosed as a diabetic, according to a committee of experts from around the world meeting at the American Diabetes Association (ADA) 69th Scientific Sessions. This measurement, they added, should become a new international standard for the diagnosis of diabetes.
"A1C is a better measurement, technically, and in terms of convenience when compared to current glucose measurements -- and A1C correlates closely with the risk of diabetic retinopathy," said David M. Nathan, MD, Diabetes Center, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts. Dr. Nathan chaired the expert committee presentation here on June 5.
There are presently 2 standard tests used to diagnose diabetes: the fasting plasma glucose test or the oral glucose tolerance test. The committee examined the correlation between long-term glycaemic elevations and neuropathic complications like retinopathy, and found that Hb A1C, measuring average blood-glucose control over the past 2 to 3 months, would be a better diagnostic tool.
"We wanted a measure that would indicate where clinical complications could ensue, and elevation above Hb A1C 6.5% is where the danger of diabetic retinopathy actually begins," Dr. Nathan noted.
For individuals with an elevated risk of developing diabetes (genetically or due to obesity), the committee noted that an Hb A1C of 6% but less than 6.5% is likely to put these individuals at highest risk.
Paul Robertson, MD, president for medicine and science of the ADA, added comments at a press briefing after the guidelines were presented. He said that his organisation will develop a task force to study the report and to assess the new recommendation. The ADA did release an announcement on June 5, officially acknowledging the potential significance of Hb A1C as a potential diagnostic tool without officially endorsing the recommendations of the committee yet.
The report of the international expert committee was published online ahead of print on June 5 at http://care.diabetesjournals.org; it will appear in the July issue of Diabetes Care.
Diabetes experts on the committee represented the ADA, the International Diabetes Federation, and the European Association for the Study of Diabetes.
By Bruce Sylvester
NEW ORLEANS -- June 6, 2009 -- A patient who reaches a glycosylated hemoglobin (Hb A1C) level of 6.5% should be diagnosed as a diabetic, according to a committee of experts from around the world meeting at the American Diabetes Association (ADA) 69th Scientific Sessions. This measurement, they added, should become a new international standard for the diagnosis of diabetes.
"A1C is a better measurement, technically, and in terms of convenience when compared to current glucose measurements -- and A1C correlates closely with the risk of diabetic retinopathy," said David M. Nathan, MD, Diabetes Center, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts. Dr. Nathan chaired the expert committee presentation here on June 5.
There are presently 2 standard tests used to diagnose diabetes: the fasting plasma glucose test or the oral glucose tolerance test. The committee examined the correlation between long-term glycaemic elevations and neuropathic complications like retinopathy, and found that Hb A1C, measuring average blood-glucose control over the past 2 to 3 months, would be a better diagnostic tool.
"We wanted a measure that would indicate where clinical complications could ensue, and elevation above Hb A1C 6.5% is where the danger of diabetic retinopathy actually begins," Dr. Nathan noted.
For individuals with an elevated risk of developing diabetes (genetically or due to obesity), the committee noted that an Hb A1C of 6% but less than 6.5% is likely to put these individuals at highest risk.
Paul Robertson, MD, president for medicine and science of the ADA, added comments at a press briefing after the guidelines were presented. He said that his organisation will develop a task force to study the report and to assess the new recommendation. The ADA did release an announcement on June 5, officially acknowledging the potential significance of Hb A1C as a potential diagnostic tool without officially endorsing the recommendations of the committee yet.
The report of the international expert committee was published online ahead of print on June 5 at http://care.diabetesjournals.org; it will appear in the July issue of Diabetes Care.
Diabetes experts on the committee represented the ADA, the International Diabetes Federation, and the European Association for the Study of Diabetes.
Tuesday
Hemoglobin as a potential source of natural regulatory oligopeptides.
Bach Institute of Biochemistry, Russian Academy of Sciences, Moscow, Russia. aaz@inbi.ras.ru
Theoretical structure-function analysis of all possible hemoglobin molecule fragments was performed to determine sites that could be potential sources of regulatory oligopeptides. Known data on bovine hemoglobin primary structure and information of the EROP-Moscow database concerning structure and functions of natural oligopeptides were used along with a computer program complex. A total of 6750 natural non-hemoglobin oligopeptides with hemoglobin fragments of 2-14 amino acid residues were found. Structures of 20 of them were completely identical to hemoglobin fragments. Most of the revealed oligopeptides exhibit properties of neuropeptides, antimicrobial agents, and hormones. A number of them exhibit functions previously not known for hemoglobin fragments. The possibility of natural formation of regulatory oligopeptides from hemoglobin and other food protein molecules, generation of the exogenous oligopeptide pool, their participation in regulation processes as well as accordance of results obtained here with the oligopeptide continuum concepts are discussed.
Theoretical structure-function analysis of all possible hemoglobin molecule fragments was performed to determine sites that could be potential sources of regulatory oligopeptides. Known data on bovine hemoglobin primary structure and information of the EROP-Moscow database concerning structure and functions of natural oligopeptides were used along with a computer program complex. A total of 6750 natural non-hemoglobin oligopeptides with hemoglobin fragments of 2-14 amino acid residues were found. Structures of 20 of them were completely identical to hemoglobin fragments. Most of the revealed oligopeptides exhibit properties of neuropeptides, antimicrobial agents, and hormones. A number of them exhibit functions previously not known for hemoglobin fragments. The possibility of natural formation of regulatory oligopeptides from hemoglobin and other food protein molecules, generation of the exogenous oligopeptide pool, their participation in regulation processes as well as accordance of results obtained here with the oligopeptide continuum concepts are discussed.
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