Vascular memory

This 2022 rodent study investigated effects of inducing hypertension for two weeks:

“Hypertension is conventionally associated with a neurohormonal activation from the sympathetic nervous and the renin-angiotensin-aldosterone systems. Angiotensin II (AngII) is a potent regulator of blood pressure, and is also a key player in hypertension development.

An initial 2-week exposure to AngII induced profound changes in cardiac and vascular remodeling, including endothelial activation, vascular inflammation and oxidant stress, all of which were maintained up to 3 weeks after AngII withdrawal. This phenotype was sustained despite early normalization of blood pressure after AngII withdrawal.

Our RNAseq pathway analysis suggests involvement of epigenetic regulators involved in methylation, such as PRC2. PCR2 complex catalyzes trimethylation of histone H3 on lysine 27 (H3K27me3), a histone mark necessary for maintaining transcriptional repression during multicellular development.

H3K27me3 AngII

Cell type-specific patterns of H3K27me3 are crucial for preserving cell identity. Consistent with this analysis, we observed a significant increase in H3K27me3 epigenetic mark in aortic tissue, intriguingly, only in both memory conditions.

Transient exposure to Ang II produces prolonged vascular remodeling with robust ACTA2 downregulation, associated with epigenetic imprinting, supporting a memory effect despite stimulus withdrawal. Future characterization of underlying AngII-dependent signaling might unveil new targets for its therapeutic modulation and reversal of this adverse legacy effect.”

https://www.frontiersin.org/articles/10.3389/fcvm.2022.854361/full “Sustained Downregulation of Vascular Smooth Muscle Acta2 After Transient Angiotensin II Infusion: A New Model of Vascular Memory”


These subjects’ ages were equivalent to a 20-year-old human:

  • How much earlier could our vascular system retain events we experienced such as epigenetic H3K27me3 increases? Teenaged, late childhood, early childhood, infancy, fetal parts of our lives?
  • How long would these vascular system memories and their continued signaling linger?
  • What experiences could change these long-lasting memories?

Icy fire

PXL_20220329_185742880

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