How IGF can save your life.
Today the world is concerned about a disease called Atherosclerosis. This disease can shorten a person's life. It can make it impossible for a person to live the full life he or she was meant to live. To this day, many experts are trying to find a solution. Could the solution lie in bioengineering?
Atherosclerosis is a pathogenic condition characterized by focal inflammatory thickening of arterial walls. It is the leading cause of cardiovascular disease (CVD), such as coronary heart disease, stroke and peripheral artery disease. Because cardiovascular disease is the leading cause of death worldwide, there have been significant ongoing efforts to develop therapeutic strategies directly aimed at eliminating atherosclerotic lesions and preventing adverse events. Nevertheless, the development of new drugs has been a challenge, and current treatment options remain limited to preventive lifestyle changes, hypolipidemic therapy, and control of risk factors such as arterial hypertension and glycemic control.
Atherosclerosis is a multifactorial disease, and our understanding of its pathogenesis has advanced considerably over the past decade. By the early 2000s, the main working hypotheses proposed as mechanisms of atherogenesis included the "delay response hypothesis" and the "oxidative modification hypothesis. These hypotheses argued that lesions are initiated when there is a subendothelial retention of lipids (low-density lipoproteins) that are modified (e.g., aggregated, oxidized) to become biologically active. Because of this aspect, atherosclerosis can begin to progress. Add to that improper nutrition, improper/overuse of anabolic steroids, and other factors. But what does this have to do with IGF?
There was a very interesting article in 2019 that looked at the potential effects of IGF-1 on atherosclerotic disease.
Insulin-like growth factor 1 (IGF-1) is a major regulator of postnatal (prepubertal and pubertal) somatic growth, mediating many effects of growth hormone (GH). Circulating IGF-1 levels peak in mid-adolescence (111-647 ng/mL) and then decrease with age. In healthy adults at age 40, its reference range is about 50-65% lower than its peak range (68-226 ng/mL or 9-30 nM). IGF-1 and its cognate peptide hormone, insulin, show similar affinities to their respective cognate receptors, but circulating IGF-1 levels are 10 times or higher. Most circulating IGF-1 molecules form complexes with IGF-binding proteins (IGFBPs) that interfere with IGF-1 binding to the insulin receptor or modulate IGF-1 binding to the IGF-1 receptor (IGF1R) [ 37 ]. ]. IGF1R is expressed in the three major cell types involved in the pathogenesis of atherosclerosis, namely endothelial cells, macrophages and SMCs. The biological effects of IGF-1 on cultured vascular endothelial cells, smooth muscle cells, and macrophages have long been described, and more recent studies have provided insight into the effects of IGF-1 on the pathogenesis of atherosclerosis.
First of all, the work and importance of IGF illustrates human mortality very well. The relationship of IGF-1 and long-term survival/mortality has been the subject of much debate and appears to depend on age, race, and gender. They followed IGF-1 levels in 1,618 elderly people in the Mayo Aging Study. Looking primarily at bioavailable IGF-1 (ratio of IGF-1 to IGFBP-3), they reported that men had a faster age-related decline in IGF-1 compared to women. A certain scientist, Sanders, in a study of 945 people over the age of 65 in a cardiovascular disease study with a mean follow-up of 11.3 years, found that baseline IGF-1 levels <70 ng/mL and higher IGF-1 variability were associated with higher mortality. Similarly, other researchers in papers have found higher mortality in patients on hemodialysis with lower serum IGF-1 levels modulated by serum albumin.
Another scientist, Schutte, performed a detailed longitudinal observational analysis as part of the PURE study among high-risk black South Africans. They reported that higher IGF-1 levels predicted lower mortality at 5 years after adjustment for IGFBP-3 and were significantly associated with maintenance of normotensive status. Interestingly, they did not observe any association between IGF-1 and CC-IMT, which could be explained by the different ethnicity of this population compared to previously published studies. It is also possible that high-risk behaviors in the PURE study population, with higher alcohol consumption, smoking, and obesity, could directly lead to lower IGF-1 levels.
Burgers went even further in a meta-analysis of 12 studies with 14,906 participants suggested a U-shaped association of IGF-1 with mortality, with increased mortality in subjects with low or low IGF-1 levels compared with average centile reference categories.
In 2007, very serious tests were conducted with animals. We will not go into detail, but the conclusions of the study are as follows:
Increased levels of IGF-1 in the bloodstream not only reduced the number of plaques but also induced phenotypic changes in plaques represented by decreased macrophage numbers, attenuation of proinflammatory cytokine expression, decreased oxidative stress, less frequent apoptosis, and increased presence of smooth muscle. cells and collagen. These observations suggest that IGF-1 may reduce inflammation and promote a more stable plaque phenotype, highlighting the therapeutic potential of IGF-1 in preventing clinical events caused by plaque vulnerability. Why is it important for us to know this about IGF? And the point is that an incorrect course and some drugs can put pressure on the lipid profile, by which the use of IGF can smooth out the harmful effects of steroids and their side effects.
The article is very large, with many aspects, but if you highlight the thesis from each study, you can conclude:
Low levels of circulating IGF-1 are associated with cardiovascular disease.
Cell-type-specific changes in the IGF-1 system in animal models are consistent with the atheroprotective effects of IGF-1.
Evidence suggests a beneficial role of IGF-1 in the pathology of atherosclerosis.
There are some people who are skeptical about bioengineering, maybe directly about IGF. So if you're interested in reading this kind of research yourself, look for the work supported by National Institutes of Health grant 5-R01-HL070241.
Today the world is concerned about a disease called Atherosclerosis. This disease can shorten a person's life. It can make it impossible for a person to live the full life he or she was meant to live. To this day, many experts are trying to find a solution. Could the solution lie in bioengineering?
Atherosclerosis is a pathogenic condition characterized by focal inflammatory thickening of arterial walls. It is the leading cause of cardiovascular disease (CVD), such as coronary heart disease, stroke and peripheral artery disease. Because cardiovascular disease is the leading cause of death worldwide, there have been significant ongoing efforts to develop therapeutic strategies directly aimed at eliminating atherosclerotic lesions and preventing adverse events. Nevertheless, the development of new drugs has been a challenge, and current treatment options remain limited to preventive lifestyle changes, hypolipidemic therapy, and control of risk factors such as arterial hypertension and glycemic control.
Atherosclerosis is a multifactorial disease, and our understanding of its pathogenesis has advanced considerably over the past decade. By the early 2000s, the main working hypotheses proposed as mechanisms of atherogenesis included the "delay response hypothesis" and the "oxidative modification hypothesis. These hypotheses argued that lesions are initiated when there is a subendothelial retention of lipids (low-density lipoproteins) that are modified (e.g., aggregated, oxidized) to become biologically active. Because of this aspect, atherosclerosis can begin to progress. Add to that improper nutrition, improper/overuse of anabolic steroids, and other factors. But what does this have to do with IGF?
There was a very interesting article in 2019 that looked at the potential effects of IGF-1 on atherosclerotic disease.
Insulin-like growth factor 1 (IGF-1) is a major regulator of postnatal (prepubertal and pubertal) somatic growth, mediating many effects of growth hormone (GH). Circulating IGF-1 levels peak in mid-adolescence (111-647 ng/mL) and then decrease with age. In healthy adults at age 40, its reference range is about 50-65% lower than its peak range (68-226 ng/mL or 9-30 nM). IGF-1 and its cognate peptide hormone, insulin, show similar affinities to their respective cognate receptors, but circulating IGF-1 levels are 10 times or higher. Most circulating IGF-1 molecules form complexes with IGF-binding proteins (IGFBPs) that interfere with IGF-1 binding to the insulin receptor or modulate IGF-1 binding to the IGF-1 receptor (IGF1R) [ 37 ]. ]. IGF1R is expressed in the three major cell types involved in the pathogenesis of atherosclerosis, namely endothelial cells, macrophages and SMCs. The biological effects of IGF-1 on cultured vascular endothelial cells, smooth muscle cells, and macrophages have long been described, and more recent studies have provided insight into the effects of IGF-1 on the pathogenesis of atherosclerosis.
First of all, the work and importance of IGF illustrates human mortality very well. The relationship of IGF-1 and long-term survival/mortality has been the subject of much debate and appears to depend on age, race, and gender. They followed IGF-1 levels in 1,618 elderly people in the Mayo Aging Study. Looking primarily at bioavailable IGF-1 (ratio of IGF-1 to IGFBP-3), they reported that men had a faster age-related decline in IGF-1 compared to women. A certain scientist, Sanders, in a study of 945 people over the age of 65 in a cardiovascular disease study with a mean follow-up of 11.3 years, found that baseline IGF-1 levels <70 ng/mL and higher IGF-1 variability were associated with higher mortality. Similarly, other researchers in papers have found higher mortality in patients on hemodialysis with lower serum IGF-1 levels modulated by serum albumin.
Another scientist, Schutte, performed a detailed longitudinal observational analysis as part of the PURE study among high-risk black South Africans. They reported that higher IGF-1 levels predicted lower mortality at 5 years after adjustment for IGFBP-3 and were significantly associated with maintenance of normotensive status. Interestingly, they did not observe any association between IGF-1 and CC-IMT, which could be explained by the different ethnicity of this population compared to previously published studies. It is also possible that high-risk behaviors in the PURE study population, with higher alcohol consumption, smoking, and obesity, could directly lead to lower IGF-1 levels.
Burgers went even further in a meta-analysis of 12 studies with 14,906 participants suggested a U-shaped association of IGF-1 with mortality, with increased mortality in subjects with low or low IGF-1 levels compared with average centile reference categories.
In 2007, very serious tests were conducted with animals. We will not go into detail, but the conclusions of the study are as follows:
Increased levels of IGF-1 in the bloodstream not only reduced the number of plaques but also induced phenotypic changes in plaques represented by decreased macrophage numbers, attenuation of proinflammatory cytokine expression, decreased oxidative stress, less frequent apoptosis, and increased presence of smooth muscle. cells and collagen. These observations suggest that IGF-1 may reduce inflammation and promote a more stable plaque phenotype, highlighting the therapeutic potential of IGF-1 in preventing clinical events caused by plaque vulnerability. Why is it important for us to know this about IGF? And the point is that an incorrect course and some drugs can put pressure on the lipid profile, by which the use of IGF can smooth out the harmful effects of steroids and their side effects.
The article is very large, with many aspects, but if you highlight the thesis from each study, you can conclude:
Low levels of circulating IGF-1 are associated with cardiovascular disease.
Cell-type-specific changes in the IGF-1 system in animal models are consistent with the atheroprotective effects of IGF-1.
Evidence suggests a beneficial role of IGF-1 in the pathology of atherosclerosis.
There are some people who are skeptical about bioengineering, maybe directly about IGF. So if you're interested in reading this kind of research yourself, look for the work supported by National Institutes of Health grant 5-R01-HL070241.
damn missed the thing...
