Transcriptional regulation is essential for the development, homeostasis, and function of all organisms. Transcription factors and epigenetic modifiers play an indispensable role by direct or indirect interaction with DNA or chromatin. Although the role of transcription factor PRDM16 in adipose, haematopoietic, skeletal, and neural cell lineage specification is well-documented, its function within the cardiovascular system has only recently gained significant attention. Similar as in adipose tissue, PRDM16 displays an asymmetric expression pattern within the cardiovascular system, where it is exclusively expressed by ventricular cardiomyocytes and endothelial and smooth muscle cells of arteries while being absent in their atrial and venous counterparts. Concordantly, an increasing number of clinical and preclinical studies have identified PRDM16 as an important multi-modal regulator of cardiovascular development and function. Moreover, aberrant PRDM16 expression has now been linked to (cardio)vascular diseases, including left ventricular non-compaction, migraine, and coronary artery disease. In this review, we give a synopsis of PRDM16's expression and function within (developing) cardiovascular tissues and provide insights into how impaired PRDM16 signalling contributes to cardiovascular disease.

Microglia perform surveillance and phagocytosis to maintain the homeostasis of the central nervous system (CNS). These processes are energetically demanding, and given the critical roles of mitochondria in providing ATP, the characteristics of the mitochondrial network can modulate microglial behavior. Although the Ca²⁺-permeable Transient Receptor Potential Vanilloid 4 (TRPV4) is known for regulating microglial morphology and migration, and it is implicated in mitochondrial calcium uptake, it is unknown whether TRPV4 affects the mitochondrial network in microglia. Our study provides evidence that TRPV4 plays a role in the integrity and complexity of the mitochondrial network in microglia. Quantification of the Mitochondrial Fragmentation and Complexity Index (MFCI) and increased pDrp1 (Ser616) showed a shift towards mitochondrial network fragmentation, and lowered complexity in Trpv4 knockout versus wild-type primary murine microglia in vitro. The distribution of mitochondria within microglia showed significant differences in density at 10–32 µm away from the nucleus. Furthermore, acute pharmacological TRPV4 inhibition with GSK2193874 did not induce significant mitochondria network fragmentation. Our findings establish TRPV4 as a regulator of mitochondrial dynamics and adaptive responses, highlighting its importance for maintaining homeostasis in microglia and the entire CNS.