Evidence for Loss of Capillary Density to be Important in Heart Disease
Loss of capillary density, and thus flow of blood through tissues, is a known feature of aging, though the causes of this change in tissue maintenance are far from completely explored. It is proposed to be quite important in loss of tissue function, particularly in organs with high metabolic demands, such as muscle and the brain. Researchers here provide evidence to suggest that this loss of capillary density is a noteworthy mediating mechanism linking the age-related impairment of heart function with the presence of chronic kidney disease. The latter is already known to correlate with impaired capillary structure in the heart, and here data from patients shows that this is a factor in the progression to heart disease.
People with chronic kidney disease have a higher risk for heart disease and heart-disease death. Coronary microvascular dysfunction, or CMD, is decreased blood flow in the small blood vessels inside the heart muscle that provide oxygen and fuel to feed the pumping heart. A new study links kidney disease to progressive heart disease via this mechanism. In healthy hearts, visualized postmortem, these blood vessels look like a tight filigree network that fills the heart muscle tissue. A diseased postmortem heart has lost much of this network. In living patients, however, those small blood vessels inside the heart muscle cannot be visualized; blood flow scans of living patients visualize only the larger, exterior coronary arteries.
Thus researchers needed an indirect way to gauge CMD. That measure is coronary flow reserve, or CFR, assessed via positron emission tomography. CFR is the maximum increase in blood flow through the coronary arteries above the normal resting volume. In a longitudinal study of 352 patients with chronic kidney disease, all with healthy heart function as measured by ejection fraction and none with signs of overt coronary artery disease, the researchers measured CFR and also measured signs of subclinical heart dysfunction. The patients were then followed a median of 4.4 years for major adverse cardiac events. A total of 108 patients had such major events, including death and hospitalization for non-fatal heart attack or heart failure.
The researchers found that CMD was a significant predictor of abnormal mechanics of the left ventricle - the heart's major pumping chamber - and a significant predictor of clinical risk of adverse cardiovascular outcomes. A statistical model called mediation analysis examined the relationship between impaired kidney function and heart disease. It showed that CMD accounted for 19 to 24 percent of left ventricle diastolic dysfunction, 19 to 42 percent of left ventricle systolic dysfunction and 32 percent of major adverse cardiovascular events. This evidence suggests that the development of severe microvascular dysfunction likely signals the transition from physiological to pathological left ventricle remodeling that increases the risk of heart failure and death in patients with chronic kidney disease.
Reminds me of this Methuselah Foundation blog article on vitamin C deficiency causing loss of capilaries in the skin:
https://www.mfoundation.org/news/can-a-local-vitamin-c-deficiency-in-the-skin-cause-atrophy-of-the-microvasculature
@jimofoz
In a way , local deficiencies or elevated values can be lumped together as metabolic considering
Article below discusses NAD percursers as a method to increase capillary density.
https://hms.harvard.edu/news/rewinding-clock
The following 3 studies taken together may help explain why mice that were given NMN in studies showed reversal of heart disease and why human heart disease studies are warranted
#1
This 2020 study, researchers provide evidence to suggest loss of capillary density is a noteworthy mediating mechanism linking the age-related impairment of heart function with chronic kidney disease which correlates with impaired capillary structure in the heart, data from patients shows that this is a factor in the progression to heart disease. Researchers found that CMD was a significant predictor of abnormal mechanics of the left ventricle (LV) the heart's major pumping chamber and a significant predictor of clinical risk of adverse cardiovascular outcomes. It showed the CMD accounted for 19 to 24 percent of left ventricle diastolic dysfunction 19 to 42 percent of left ventricle systolic dysfunction and 32 percent of major adverse cardiovascular events.
#2
In a 2017 study NMN was administered to KXN-KO mice that had increased left ventricular (LV) wall thickness and decreased left ventricle end-systolic diameter (LVESD) measured by echocardiography. NMN restored cardiac function to near normal levels. NMN supplementation in the FXN-KO mice normalized the defective cardiac contractility and diastolic function in this model. Cardiac efficiency in the FXN-KO was normalized with NMN supplementation
#3
In a 2018 study conducted by scientists lead by Dr. Sinclair conducted a number of experiments and discovered that blood flow declines as the result of endothelial cells losing a protein known as SIRT1. Some readers may recall that the SIRT1 protein has been shown to extend lifespan in yeast and mice, and it plays an important role in metabolism. The study results show that NAD+ and SIRT1 facilitate crosstalk between the endothelial cells in the blood vessel walls and the muscle cells. The experiment shows that in young mice, SIRT1 signaling activates, which leads to the creation of new blood capillaries, the smallest blood vessels that supply oxygen and nutrients to the tissues. However, the study strongly suggests that as NAD+ and SIRT1 levels decline during aging, blood flow decreases, which leaves muscle tissue starved of oxygen and nutrients, thus leading to sarcopenia. NMN increases NAD which restores the number and density of blood capillaries to levels seen in young mice. The blood flow to muscles was increased and was significantly higher than that observed in control mice of the same age.
For those who are concerned about where the NMN is made. Most of the NMN powder available today is made in China who is having health issues currently There are some providers that state their NMN is not made in China so you will have a choice if that is important to you.
@Jennifer
I believe there are many self-experimenting people out there, including myself, who take NAD+ precursors. How hard would it be to lump them together for human studies?