Vessel formation

The building of new blood vessels — restorative when it perfuses healthy tissue, pathological when it feeds disease.

Vessel growth signal increases it.

Ferrara 2004, Endocr Rev 25:581 — VEGF is an endothelial-specific mitogen; VEGF/VEGFR signaling drives endothelial proliferation, migration and new-vessel formation. PMID 15294883

Hypoxia response increases it.

Hypoxia is the signal that builds new vessels, and HIF-1 is the transducer: it is the most potent inducer of the genes encoding VEGF, the glycolytic enzymes and erythropoietin, and it is the central mediator of angiogenesis under low oxygen (PMC4656338, PMC11079266). Shown causally rather than by association — knockdown of either HIF-1α or HIF-2α strikingly attenuated hypoxia-induced VEGF production by endothelial cells and their colony and tube formation (PMC6366960). This lane runs alongside the VEGF one because HIF is upstream of it, not parallel to it. PMC4656338

Mitochondrial energy reduces it.

The body does not remodel delivery and utilization systems independently: PGC-1-alpha promotes VEGF expression, linking angiogenesis and mitochondrial adaptation so that oxygen delivery and oxygen utilization scale together. The causal pair is clean: overexpression of PGC-1-alpha increases skeletal muscle capillarisation, while deletion prevents exercise-induced angiogenesis — in part through PGC-1-alpha-regulated secretion of VEGF. Add it and vessels grow; remove it and exercise cannot grow them. And the dependence is stated as a rule of muscle architecture: the primary determinants of muscle fiber capillary density ARE fiber size and oxidative capacity — that is, mitochondrial volume. Highly oxidative fibers have both more mitochondria and greater capillary density; the vasculature is built to match the demand. Human corroboration in the elderly: lifelong endurance-trained subjects aged 71 had 27 percent more capillaries per fiber than untrained age-matched controls, alongside higher oxidative enzyme activities, and cycled 35 percent longer before exhaustion. What this changes: mitochondria and new vessels look like parallel drivers of physical performance. They are coupled, and PGC-1-alpha - also a driver of this outcome - is the coupler. doi 10.1371/journal.pone.0028290 · PMC9949767

It increases Physical performance.

Increased capillary density is named as a major peripheral adaptation to endurance training, making it easier for blood and hemoglobin to travel close to working fibers and release oxygen — so oxygen extraction fraction rises as a typical training adaptation. Human, and it works in the old: in a training study including older and young adults, indices of capillarisation increased 30-40 percent in the older group and 20-30 percent in the young — the older group adapted more, and both showed capillary angiogenesis with improved mitochondrial respiratory capacity and a greater maximal a-vO2 difference. capillarity is a peripheral factor — see the Contractility → Aerobic Capacity link, where central delivery is stated to be the primary limit for whole-body exercise. (Study on file: PMC5735290 · doi 10.1016/j.cophys.2019.04.005 · doi 10.1111/sms.14442 (Hellsten 2024) · doi 10.3389/fphys.2025.1681184 ·. doi 10.1016/j.cophys.2019.04.005 · PMC5735290

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