Multiscale interactions in cardiovascular homeostasis and remodeling: from molecular coupling to organelle and multicellular networks.

Cardiovascular homeostasis is increasingly understood not as the output of isolated pathways, but as an emergent and history-dependent property of interactions across biological scales. Cutting-edge technologies have revealed coupling between transcription and metabolism, signaling within molecular microdomains, organelle networks, communication between cardiomyocytes and non-myocytes, neurovascular regulation, and interorgan interactions. This special issue brings together five perspectives that examine how such interactions preserve physiological function and, under stress, redirect the cardiovascular system toward adaptation or disease. As a representative multiscale example, this Editorial highlights hierarchical mitochondrial quality control. Biogenesis, fusion-fission dynamics, proteostasis, mitochondria-derived vesicles, organelle contacts, and mitophagy form a graded defense network that matches the response to the burden and location of damage. The same network connects mitochondrial dysfunction to innate immunity and tissue remodeling. Defining directionality, spatial context, temporal order, and flux within these interactions will be essential for converting descriptive interaction maps into causal physiology and selective therapies.