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Cardiology |
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| 11 Feb 2009 | Viewed: 10 | |
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A long and healthy life for mice lacking the protein AT1A
Ariela Benigni and colleagues, at the "Mario Negri" Institute for
Pharmacological Research, Italy, have found that mice lacking the
protein AT1A live substantially longer than normal mice. As drugs that
antagonize AT1A are currently used to treat high blood pressure and
heart failure, the authors suggest that future studies should
investigate whether such drugs prolong life in humans. Further analysis
revealed that the increased lifespan in mice lacking AT1A was likely a
result of decreased oxidative damage to cells, a key factor in ageing,
and increased levels of genes involved in cell survival (such as
Sirt3).
TITLE: Disruption of the Ang II type 1 receptor promotes longevity in mice
AUTHOR CONTACT:
Ariela Benigni
"Mario Negri" Institute for Pharmacological Research, Bergamo, Italy.
View the PDF of this article at: https://www.the-jci.org/article.php?id=36703
HEMATOLOGY: New signposts to the way out of the bone marrow for blood cell precursors
Understanding what molecular pathways control the release of hematopoietic stem cells
(i.e., the stem cells that give rise to all blood cells) from the bone
marrow has immense relevance to a number of clinical situations,
including stem cell transplantation and post-chemotherapy treatment
regimens. New insight into the molecules involved in regulating the
movement of human hematopoietic progenitor cells from the bone marrow,
provided by the work of Tsvee Lapidot and colleagues, at the Weizmann
Institute of Science, Israel, might provide clues to developing new
ways to enhance stem cell release from the bone marrow.
In the study, CD34+ hematopoietic progenitor cells in the
bloodstream of healthy individuals were found to express higher levels
of the protein MT1-MMP and lower levels of the protein RECK than their
precursor cells in the bone marrow. Further, when healthy individuals
were treated with a drug that stimulates the release of hematopoietic
progenitor cells from the bone marrow, the circulating cells expressed
even higher levels of MT1-MMP. Further analysis in mice with bone
marrow reconstituted with human cells, revealed that blocking MT1-MMP
function impaired the release of human hematopoietic progenitor cells
from the bone marrow and that blocking RECK function enhanced the
release of these cells. Additional experiments determined that MT1-MMP
promotes the release of hematopoietic progenitor cells from the bone
marrow by cleaving a protein known as CD44. The authors conclude that
MT1-MMP and RECK have opposing roles in the control of human
hematopoietic progenitor cell egress from the bone marrow.
TITLE: MT1-MMP and RECK are involved in human CD34+ progenitor cell retention, egress, and mobilization
AUTHOR CONTACT:
Tsvee Lapidot
Weizmann Institute of Science, Rehovot, Israel.
View the PDF of this article at: https://www.the-jci.org/article.php?id=36541
HEMATOLOGY: Explaining how the drug eptifibatide can have unintended consequences
The drug eptifibatide interferes with blood clotting and is
used to treat a number of serious heart conditions associated with a
high risk of heart attack. Despite the effectiveness of eptifibatide
and other related drugs, in a few individuals they cause serious side
effects, including thrombocytopenia (a deficiency in blood cells known
as platelets, which are important for blood clotting). Peter Newman and
colleagues, at the BloodCenter of Wisconsin, Milwaukee, have now
provided new insight into the molecular mechanisms by which
eptifibatide induces thrombocytopenia.
Eptifibatide works by antagonizing a protein complex known as
integrin alpha-IIb-beta-3. The rare cases of thrombocytopenia in
patients treated with eptifibatide are caused by antibodies, generated
by the immune system of the patients, that recognize the drug bound to
integrin alpha-IIb-beta-3. In the study, the authors analyzed the
effects of patient serum containing an alpa-IIb-beta-3-specific,
eptifibatide-dependent antibody on normal human platelets. In the
presence of eptifibatide, the antibodies caused the platelets to become
activated. Further analysis revealed that activation was mediated via a
signaling pathway initiated by Fc-gamma-RIIa and beta-3 integrin. These
data provide a mechanism that explains how alpa-IIb-beta-3-specific,
eptifibatide-dependent antibodies can cause thrombocytopenia.
TITLE: Eptifibatide-induced thrombocytopenia and thrombosis in
humans require Fc-gamma-RIIa and the integrin beta-3 cytoplasmic domain
AUTHOR CONTACT:
Peter J. Newman
BloodCenter of Wisconsin, Milwaukee, Wisconsin, USA.
View the PDF of this article at: https://www.the-jci.org/article.php?id=36745
PULMONARY: The protein FGF2: a new target in the fight against pulmonary hypertension?
Pulmonary hypertension is the name given to the potentially
fatal condition of high blood pressure in the vessels that carry blood
from the heart to the lung, where the blood replenishes its supply of
oxygen, and back. It is characterized by the proliferation of a subset
of cells in the wall of the blood vessel going from the heart to the
lung that are known as pulmonary artery smooth muscle cells (PA-SMCs).
While the lung endothelium (the layer of cells that lines the blood
vessels going to and from the lung) is thought to influence this
process, its role has not been well understood. In a new study, Saadia
Eddahibi and colleagues, at INSERUM U841, France, have revealed the
role of a specific protein, FGF2, in the endothelial response during
pulmonary hypertension.
The lung endothelium of patients with pulmonary hypertension
had increased FGF2 production compared to healthy controls. Moreover,
PA-SMCs treated with media from cultured patient endothelial cells
experienced greater proliferation than PA-SMCs treated with media from
healthy control individuals. This proliferation was blocked by
approaches that inhibited FGF2, both in cultured cells and in a rat
model of pulmonary hypertension. The authors therefore conclude that
FGF2 may serve as a novel target in the treatment of pulmonary
hypertension.
TITLE: Endothelial-derived FGF2 contributes to the progression of pulmonary hypertension in humans and rodents
AUTHOR CONTACT:
Saadia Eddahibi
INSERM U841, Créteil, France.
View the PDF of this article at: https://www.the-jci.org/article.php?id=35070
PULMONARY: Immune cells contribute to chronic obstructive pulmonary disease (COPD)
Chronic obstructive pulmonary disease (COPD) is a progressive
disease of the lung and the fourth leading cause of death in the United
States. Although recent studies suggest immune cells known as
lymphocytes contribute to the chronic airway inflammation that is
associated with COPD, there is no evidence that they are involved in
the development of the disease. However, Michael Borchers and
colleagues, at the University of Cincinnati College of Medicine,
Cincinnati, have now determined that a subset of lymphocytes known as
CTLs do contribute to the development of COPD-like disease in mice.
In the study, in vivo and in vitro exposure of the lining of
the mouse airway to cigarette smoke induced the airway lining to
express a protein known as RAET1, which binds the protein NKG2D on
CTLs, activating them. Consistent with CTLs having a role in the
development of COPD, induction of RAET1 expression in the lining of
mouse airways, induced COPD-like disease that was reversible by
blocking NKG2D. As the authors found increased expression of a protein
that binds human NKG2D in lung tissue from smokers with normal lung
function, and current and former smokers with COPD, but not in lung
tissue from individuals who had never smoked, they suggest that
persistent expression of proteins that bind NKG2D in the cells lining
the lungs and airways contributes to the development of COPD via
activation of CTLs.
TITLE: Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like disease
AUTHOR CONTACT:
Michael T. Borchers
University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
View the PDF of this article at: https://www.the-jci.org/article.php?id=34462
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Article adapted by Medical News Today from original press release.
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| News Source: Medical News Today |
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