Preventing developmental origins of cardiovascular disease: Hydrogen sulfide as a potential target?

The cardiovascular system can be programmed by a diversity of early-life insults, leading to cardiovascular disease (CVD) in adulthood. This notion is now termed developmental origins of health and disease (DOHaD). Emerging evidence indicates hydrogen sulfide (H₂S), a crucial regulator of cardiovascular homeostasis, plays a pathogenetic role in CVD of developmental origins. Conversely, early H₂S-based interventions have proved beneficial in preventing adult-onset CVD in animal studies via reversing programming processes by so-called reprogramming. The focus of this review will first summarize the current knowledge on H₂S implicated in cardiovascular programming. This will be followed by supporting evidence for the links between H₂S signaling and underlying mechanisms of cardiovascular programming, such as oxidative stress, nitric oxide deficiency, dysregulated nutrient-sensing signals, activation of the renin–angiotensin system, and gut microbiota dysbiosis. It will also provide an overview from animal models regarding how H₂S-based reprogramming interventions, such as precursors of H₂S and H₂S donors, may prevent CVD of developmental origins. A better understanding of cardiovascular programming and recent advances in H₂S-based interventions might provide the answers to bring down the global burden of CVD.