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Interesting article here from the American Heart Association.
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newsroom.heart.org
"Using two-dimensional ultrasound imaging, researchers found that the left ventricle, the heart's main pumping chamber, was significantly weaker during contraction (systolic function) in those taking anabolic steroids compared to the non-steroid users.
Seventy-one percent of the anabolic steroid users who were on-drug at the time of evaluation had a low pumping capacity (less than 52 percent) whereas off-drug users had largely normal pumping capacity. In contrast, researchers found that only two of the non-users had a low pumping capacity.
Diastolic function, which is when the left ventricle relaxes and fills with blood, was impaired both for on-drug and off-drug anabolic steroid users. The researchers said this suggests a more permanent heart problem."
“Compared to non-users, anabolic steroid users displayed both higher systolic and diastolic blood pressure as well as a higher prevalence of levels of bad (LDL) cholesterol in their blood,” said Aaron Baggish, M.D., study co-lead author and associate director of the cardiovascular performance program at Massachusetts General Hospital in Boston."
“It is critical that clinicians become aware of the long-term risks of anabolic steroid use on the heart. Most people relate anabolic steroids to cheating among athletes and fail to realize that there is a large population of men who have developed dependence upon these drugs, but who are not readily visible. The oldest members of this population are only now reaching middle age,” said Harrison Pope, Jr., M.D., the study’s other co-lead author and professor of psychiatry at Harvard Medical School"
“Clinicians need to know that there may be a marked increase in anabolic steroid-related cardiac pathology as this population moves into later middle-age and beyond,” said Pope who is also director of the Biological Psychiatry Laboratory at McLean Hospital, Harvard’s largest teaching hospital in psychiatry.
Other co-authors are Rory B. Weiner, M.D.; Gen Kanayama, M.D., Ph.D.; James I. Hudson, M.D.; Sc.D.; Michael Lu, M.D.; and Udo Hoffman, M.D., M.P.H. Author disclosures are on the manuscript.
A grant from the National Institutes on Drug Abuse funded the study."
CHIR99021 and fibroblast growth factor 1 enhance the regenerative potency of human cardiac muscle patch after myocardial infarction in mice
We have shown that genetic overexpression of cell cycle proteins can increase the proliferation of transplanted cardiomyocytes derived from human indu…
www.sciencedirect.com
Abstract
Background
We have shown that genetic overexpression of cell cycle proteins can increase the proliferation of transplanted cardiomyocytes derived from human induced-pluripotent stem cells (hiPSC-CMs) in animal models of myocardial infarction (MI). Here, we introduce a new, non-genetic approach to promote hiPSC-CM cell cycle activity and proliferation in transplanted human cardiomyocyte patches (hCMPs).
Methods
Mice were randomly distributed into 5 experimental groups (n = 10 per group). One group underwent Sham surgery, and the other 4 groups underwent MI induction surgery followed by treatment with hCMPs composed of hiPSC-CMs and nanoparticles that contained CHIR99021 and FGF1 (the NPCF-hCMP group), with hCMPs composed of hiPSC-CMs and empty nanoparticles (the NPE-hCMP group); with patches containing the CHIR99021/FGF-loaded nanoparticles but lacking hiPSC-CMs (the NPCF-Patch group), or patches lacking both the nanoparticles and cells (the E-Patch group). Cell cycle activity was evaluated via Ki67 and Aurora B expression, bromodeoxyuridine incorporation, and phosphorylated histone 3 levels (immunofluorescence); engraftment via human cardiac troponin T or human nuclear antigen expression (immunofluorescence) and bioluminescence imaging; cardiac function via echocardiography; infarct size and wall thickness via histology; angiogenesis via isolectin B4 expression (immunofluorescence); and apoptosis via TUNEL and caspace 3 expression (immunofluorescence).
Results
Combined CHIR99021- and FGF1-treatment significantly increased hiPSC-CM cell cycle activity both in cultured cells (by 4- to 6-fold) and in transplanted hCMPs, and compared to treatment with NPE-hCMPs, NPCF-hCMP transplantation increased hiPSC-CM engraftment by ~4-fold and was associated with significantly better measurements of cardiac function, infarct size, wall thickness, angiogenesis, and hiPSC-CM apoptosis four weeks after MI induction.
Conclusions
Nanoparticle-mediated CHIR99021 and FGF1 delivery promotes hiPSC-CM cell cycle activity and proliferation, as well as the engraftment and regenerative potency of transplanted hCMPs, in a mouse MI model.
